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Volume 14
Issue 8
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Viruses, Volume 14, Issue 8 (August 2022) – 248 articles

Cover Story (view full-size image): Many of the proteins made by RNA viruses, including Coxsackievirus, Norovirus and SARS-CoV-2, end in a C-terminal ΦQ motif because they are excised by 3C protease from a precursor polyprotein. In this issue, Luptak and colleagues reveal that this ΦQ motif is a C-terminal degron recognized by the E3 ligase TRIM7. TRIM7 targets ΦQ-containing proteins for proteasomal degradation in a mechanism reminiscent of the N-end rule and which allows it to potently inhibit viral replication. However, as TRIM7 is not immune regulated and has restricted tissue expression, its natural function may not be as a viral restriction factor. View this paper
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24 pages, 848 KiB  
Article
COVID-19 Modeling Outcome versus Reality in Sweden
by Marcus Carlsson and Cecilia Söderberg-Nauclér
Viruses 2022, 14(8), 1840; https://doi.org/10.3390/v14081840 - 22 Aug 2022
Cited by 4 | Viewed by 2167
Abstract
It has been very difficult to predict the development of the COVID-19 pandemic based on mathematical models for the spread of infectious diseases, and due to major non-pharmacological interventions (NPIs), it is still unclear to what extent the models would have fit reality [...] Read more.
It has been very difficult to predict the development of the COVID-19 pandemic based on mathematical models for the spread of infectious diseases, and due to major non-pharmacological interventions (NPIs), it is still unclear to what extent the models would have fit reality in a “do nothing” scenario. To shed light on this question, the case of Sweden during the time frame from autumn 2020 to spring 2021 is particularly interesting, since the NPIs were relatively minor and only marginally updated. We found that state of the art models are significantly overestimating the spread, unless we assume that social interactions significantly decrease continuously throughout the time frame, in a way that does not correlate well with Google-mobility data nor updates to the NPIs or public holidays. This leads to the question of whether modern SEIR-type mathematical models are unsuitable for modeling the spread of SARS-CoV-2 in the human population, or whether some particular feature of SARS-CoV-2 dampened the spread. We show that, by assuming a certain level of pre-immunity to SARS-CoV-2, we obtain an almost perfect data-fit, and discuss what factors could cause pre-immunity in the mathematical models. In this scenario, a form of herd-immunity under the given restrictions was reached twice (first against the Wuhan-strain and then against the alpha-strain), and the ultimate decline in cases was due to depletion of susceptibles rather than the vaccination campaign. Full article
(This article belongs to the Special Issue Transmission Dynamics of Coronavirus Disease)
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16 pages, 5562 KiB  
Article
Chikungunya Virus E2 Structural Protein B-Cell Epitopes Analysis
by João Paulo da Cruz Silva, Marielton dos Passos Cunha, Shahab Zaki Pour, Vitor Renaux Hering, Daniel Ferreira de Lima Neto and Paolo Marinho de Andrade Zanotto
Viruses 2022, 14(8), 1839; https://doi.org/10.3390/v14081839 - 22 Aug 2022
Cited by 2 | Viewed by 2218
Abstract
The Togaviridae family comprises a large and diverse group of viruses responsible for recurrent outbreaks in humans. Within this family, the Chikungunya virus (CHIKV) is an important Alphavirus in terms of morbidity, mortality, and economic impact on humans in different regions of the [...] Read more.
The Togaviridae family comprises a large and diverse group of viruses responsible for recurrent outbreaks in humans. Within this family, the Chikungunya virus (CHIKV) is an important Alphavirus in terms of morbidity, mortality, and economic impact on humans in different regions of the world. The objective of this study was to perform an IgG epitope recognition of the CHIKV’s structural proteins E2 and E3 using linear synthetic peptides recognized by serum from patients in the convalescence phase of infection. The serum samples used were collected in the state of Sergipe, Brazil in 2016. Based on the results obtained using immunoinformatic predictions, synthetic B-cell peptides corresponding to the epitopes of structural proteins E2 and E3 of the CHIKV were analyzed by the indirect peptide ELISA technique. Protein E2 was the main target of the immune response, and three conserved peptides, corresponding to peptides P3 and P4 located at Domain A and P5 at the end of Domain B, were identified. The peptides P4 and P5 were the most reactive and specific among the 11 epitopes analyzed and showed potential for use in serological diagnostic trials and development and/or improvement of the Chikungunya virus diagnosis and vaccine design. Full article
(This article belongs to the Special Issue RNA Viruses and Antibody Response)
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17 pages, 4301 KiB  
Article
IHNV Infection Induces Strong Mucosal Immunity and Changes of Microbiota in Trout Intestine
by Zhenyu Huang, Mengting Zhan, Gaofeng Cheng, Ruiqi Lin, Xue Zhai, Haiou Zheng, Qingchao Wang, Yongyao Yu and Zhen Xu
Viruses 2022, 14(8), 1838; https://doi.org/10.3390/v14081838 - 22 Aug 2022
Cited by 12 | Viewed by 2277
Abstract
The fish intestinal mucosa is among the main sites through which environmental microorganisms interact with the host. Therefore, this tissue not only constitutes the first line of defense against pathogenic microorganisms but also plays a crucial role in commensal colonization. The interaction between [...] Read more.
The fish intestinal mucosa is among the main sites through which environmental microorganisms interact with the host. Therefore, this tissue not only constitutes the first line of defense against pathogenic microorganisms but also plays a crucial role in commensal colonization. The interaction between the mucosal immune system, commensal microbiota, and viral pathogens has been extensively described in the mammalian intestine. However, very few studies have characterized these interactions in early vertebrates such as teleosts. In this study, rainbow trout (Oncorhynchus mykiss) was infected with infectious hematopoietic necrosis virus (IHNV) via a recently developed immersion method to explore the effects of viral infection on gut immunity and microbial community structure. IHNV successfully invaded the gut mucosa of trout, resulting in severe tissue damage, inflammation, and an increase in gut mucus. Moreover, viral infection triggered a strong innate and adaptive immune response in the gut, and RNA−seq analysis indicated that both antiviral and antibacterial immune pathways were induced, suggesting that the viral infection was accompanied by secondary bacterial infection. Furthermore, 16S rRNA sequencing also revealed that IHNV infection induced severe dysbiosis, which was characterized by large increases in the abundance of Bacteroidetes and pathobiont proliferation. Moreover, the fish that survived viral infection exhibited a reversal of tissue damage and inflammation, and their microbiome was restored to its pre−infection state. Our findings thus demonstrated that the relationships between the microbiota and gut immune system are highly sensitive to the physiological changes triggered by viral infection. Therefore, opportunistic bacterial infection must also be considered when developing strategies to control viral infection. Full article
(This article belongs to the Special Issue State-of-the-Art Aquatic Viruses Research in China)
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25 pages, 8498 KiB  
Article
Predicting Epitope Candidates for SARS-CoV-2
by Akshay Agarwal, Kristen L. Beck, Sara Capponi, Mark Kunitomi, Gowri Nayar, Edward Seabolt, Gandhar Mahadeshwar, Simone Bianco, Vandana Mukherjee and James H. Kaufman
Viruses 2022, 14(8), 1837; https://doi.org/10.3390/v14081837 - 21 Aug 2022
Cited by 3 | Viewed by 2233
Abstract
Epitopes are short amino acid sequences that define the antigen signature to which an antibody or T cell receptor binds. In light of the current pandemic, epitope analysis and prediction are paramount to improving serological testing and developing vaccines. In this paper, known [...] Read more.
Epitopes are short amino acid sequences that define the antigen signature to which an antibody or T cell receptor binds. In light of the current pandemic, epitope analysis and prediction are paramount to improving serological testing and developing vaccines. In this paper, known epitope sequences from SARS-CoV, SARS-CoV-2, and other Coronaviridae were leveraged to identify additional antigen regions in 62K SARS-CoV-2 genomes. Additionally, we present epitope distribution across SARS-CoV-2 genomes, locate the most commonly found epitopes, and discuss where epitopes are located on proteins and how epitopes can be grouped into classes. The mutation density of different protein regions is presented using a big data approach. It was observed that there are 112 B cell and 279 T cell conserved epitopes between SARS-CoV-2 and SARS-CoV, with more diverse sequences found in Nucleoprotein and Spike glycoprotein. Full article
(This article belongs to the Special Issue SARS-CoV-2 Genomics)
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23 pages, 1791 KiB  
Article
Cellular Chondroitin Sulfate and the Mucin-like Domain of Viral Glycoprotein C Promote Diffusion of Herpes Simplex Virus 1 While Heparan Sulfate Restricts Mobility
by Yara Abidine, Lifeng Liu, Oskar Wallén, Edward Trybala, Sigvard Olofsson, Tomas Bergström and Marta Bally
Viruses 2022, 14(8), 1836; https://doi.org/10.3390/v14081836 - 21 Aug 2022
Cited by 6 | Viewed by 2252
Abstract
The diffusion of viruses at the cell membrane is essential to reach a suitable entry site and initiate subsequent internalization. Although many viruses take advantage of glycosaminoglycans (GAG) to bind to the cell surface, little is known about the dynamics of the virus–GAG [...] Read more.
The diffusion of viruses at the cell membrane is essential to reach a suitable entry site and initiate subsequent internalization. Although many viruses take advantage of glycosaminoglycans (GAG) to bind to the cell surface, little is known about the dynamics of the virus–GAG interactions. Here, single-particle tracking of the initial interaction of individual herpes simplex virus 1 (HSV-1) virions reveals a heterogeneous diffusive behavior, regulated by cell-surface GAGs with two main diffusion types: confined and normal free. This study reports that different GAGs can have competing influences in mediating diffusion on the cells used here: chondroitin sulfate (CS) enhances free diffusion but hinders virus attachment to cell surfaces, while heparan sulfate (HS) promotes virus confinement and increases entry efficiency. In addition, the role that the viral mucin-like domains (MLD) of the HSV-1 glycoprotein C plays in facilitating the diffusion of the virus and accelerating virus penetration into cells is demonstrated. Together, our results shed new light on the mechanisms of GAG-regulated virus diffusion at the cell surface for optimal internalization. These findings may be extendable to other GAG-binding viruses. Full article
(This article belongs to the Section Human Virology and Viral Diseases)
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19 pages, 2936 KiB  
Article
Properties of Adenovirus Vectors with Increased Affinity to DSG2 and the Potential Benefits of Oncolytic Approaches and Gene Therapy
by Nora A. Bahlmann, Raphael L. Tsoukas, Sebastian Erkens, Hongjie Wang, Franziska Jönsson, Malik Aydin, Ella A. Naumova, André Lieber, Anja Ehrhardt and Wenli Zhang
Viruses 2022, 14(8), 1835; https://doi.org/10.3390/v14081835 - 21 Aug 2022
Cited by 5 | Viewed by 2150
Abstract
Carcinomas are characterized by a widespread upregulation of intercellular junctions that create a barrier to immune response and drug therapy. Desmoglein 2 (DSG2) represents such a junction protein and serves as one adenovirus receptor. Importantly, the interaction between human adenovirus type 3 (Ad3) [...] Read more.
Carcinomas are characterized by a widespread upregulation of intercellular junctions that create a barrier to immune response and drug therapy. Desmoglein 2 (DSG2) represents such a junction protein and serves as one adenovirus receptor. Importantly, the interaction between human adenovirus type 3 (Ad3) and DSG2 leads to the shedding of the binding domain followed by a decrease in the junction protein expression and transient tight junction opening. Junction opener 4 (JO-4), a small recombinant protein derived from the Ad3 fiber knob, was previously developed with a higher affinity to DSG2. JO-4 protein has been proven to enhance the effects of antibody therapy and chemotherapy and is now considered for clinical trials. However, the effect of the JO4 mutation in the context of a virus remains insufficiently studied. Therefore, we introduced the JO4 mutation to various adenoviral vectors to explore their infection properties. In the current experimental settings and investigated cell lines, the JO4-containing vectors showed no enhanced transduction compared with their parental vectors in DSG2-high cell lines. Moreover, in DSG2-low cell lines, the JO4 vectors presented a rather weakened effect. Interestingly, DSG2-negative cell line MIA PaCa-2 even showed resistance to JO4 vector infection, possibly due to the negative effect of JO4 mutation on the usage of another Ad3 receptor: CD46. Together, our observations suggest that the JO4 vectors may have an advantage to prevent CD46-mediated sequestration, thereby achieving DSG2-specific transduction. Full article
(This article belongs to the Special Issue New Aspects of Adenoviral Vaccine Vectors and Adenoviral Gene Therapy)
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14 pages, 3240 KiB  
Article
ASFV Gene A151R Is Involved in the Process of Virulence in Domestic Swine
by Elizabeth Ramirez-Medina, Elizabeth Vuono, Sarah Pruitt, Ayushi Rai, Nallely Espinoza, Alyssa Valladares, Edward Spinard, Ediane Silva, Lauro Velazquez-Salinas, Douglas P. Gladue and Manuel V. Borca
Viruses 2022, 14(8), 1834; https://doi.org/10.3390/v14081834 - 21 Aug 2022
Cited by 7 | Viewed by 2473
Abstract
African swine fever virus (ASFV) is the etiological agent of a swine pandemic affecting a large geographical area extending from Central Europe to Asia. The viral disease was also recently identified in the Dominican Republic and Haiti. ASFV is a structurally complex virus [...] Read more.
African swine fever virus (ASFV) is the etiological agent of a swine pandemic affecting a large geographical area extending from Central Europe to Asia. The viral disease was also recently identified in the Dominican Republic and Haiti. ASFV is a structurally complex virus with a large dsDNA genome that encodes for more than 150 genes. Most of these genes have not been experimentally characterized. One of these genes, A151R, encodes for a nonstructural protein and has been reported to be required for the replication of a Vero-cell-adapted ASFV strain. Here, we evaluated the role of the A151R gene in the context of the highly virulent field isolate Georgia 2010 (ASFV-G) during virus replication in swine macrophage cell cultures and during experimental infection in swine. We show that the recombinant virus ASFV-G-∆A151R, harboring a deletion of the A151R gene, replicated in swine macrophage cultures as efficiently as the parental virus ASFV-G, indicating that the A151R gene is not required for ASFV replication in swine macrophages. Interestingly, experimental infection of domestic pigs demonstrated that ASFV-G-∆A151R had a decreased replication rate and produced a drastic reduction in virus virulence. Animals were intramuscularly inoculated with 102 HAD50 of ASFV-G-∆A151R and compared with pigs receiving a similar dose of virulent ASFV-G. All ASFV-G-infected pigs developed an acute lethal form of the disease, while those inoculated with ASFV-G-∆A151R remained healthy during the 28-day observational period, with the exception of only one showing a protracted, but fatal, form of the disease. All ASFV-G-∆A151R surviving animals presented protracted viremias with lower virus titers than those detected in ASFV-G-infected animals. In addition, three out of the four animals surviving the infection with ASFV-G-∆A151R were protected against the challenge with the virulent parental virus ASFV-G. This is the first report indicating that the ASFV A151R gene is involved in virus virulence in domestic swine, suggesting that its deletion may be used to increase the safety profile of currently experimental vaccines. Full article
(This article belongs to the Special Issue Endemic and Emerging Swine Viruses 2022)
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15 pages, 756 KiB  
Article
HIV but Not CMV Replication Alters the Blood Cytokine Network during Early HIV Infection in Men
by Christophe Vanpouille, Alan Wells, Jennifer M. Dan, Stephen A. Rawlings, Susan Little, Wendy Fitzgerald, Leonid Margolis and Sara Gianella
Viruses 2022, 14(8), 1833; https://doi.org/10.3390/v14081833 - 21 Aug 2022
Viewed by 1483
Abstract
Objective: CMV coinfection contributes to sustained immune activation in people with chronic HIV. In particular, asymptomatic CMV shedding in semen has been associated with increased local and systemic immune activation, even during suppressive antiretroviral therapy (ART). However, the effect of seminal CMV shedding [...] Read more.
Objective: CMV coinfection contributes to sustained immune activation in people with chronic HIV. In particular, asymptomatic CMV shedding in semen has been associated with increased local and systemic immune activation, even during suppressive antiretroviral therapy (ART). However, the effect of seminal CMV shedding in people with HIV in the earliest phase of HIV infection is not known. Methods: Using Luminex, we measured the concentration of 34 cytokines in the blood plasma of sixty-nine men who had sex with men with or without HIV and in subgroups of CMV shedders vs. non-shedders. Differences in blood plasma cytokines between groups were investigated using the multivariate supervised partial least squares discriminant analysis method. Results: Independently of CMV, we found that concentrations of IP-10, MIG, MCP-1, I-TAC 10, IL-16, and MIP-1β were modulated in the earliest phase of HIV infection compared with control individuals without HIV. In people with HIV, there was no difference in blood cytokines among CMV shedders vs. non-shedders. Conclusion: In early/acute HIV infection, asymptomatic CMV shedding in semen does not drive additional cytokine changes in blood. Early ART initiation should remain the priority, while the added benefit of CMV suppression during the various stages of HIV infection needs to be further investigated. Full article
(This article belongs to the Special Issue The Role of Cytokines in HIV Infection)
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12 pages, 2639 KiB  
Article
Juvenile Wels Catfish (Silurus glanis) Display Age-Related Mortality to European Catfish Virus (ECV) under Experimental Conditions
by Flóra Abonyi, Ádám Varga, Boglárka Sellyei, Edit Eszterbauer and Andor Doszpoly
Viruses 2022, 14(8), 1832; https://doi.org/10.3390/v14081832 - 21 Aug 2022
Cited by 2 | Viewed by 1509
Abstract
We have limited knowledge about the course of the European catfish virus (ECV) infection in different age groups of wels catfish (Silurus glanis). The results of this study demonstrate that an ECV strain isolated from the brown bullhead (Ameiurus nebulosus [...] Read more.
We have limited knowledge about the course of the European catfish virus (ECV) infection in different age groups of wels catfish (Silurus glanis). The results of this study demonstrate that an ECV strain isolated from the brown bullhead (Ameiurus nebulosus) in Hungary could cause devastating losses among juvenile wels catfish. Furthermore, the age-related mortality rate following ECV infection was investigated in three virus challenge experiments at two different virus dosages. Eight-week-old (ca. 3 g), ten-week-old (ca. 8 g), and sixteen-week-old (ca. 55 g) catfish were infected with ECV at 21°C. In the youngest age group, 96% (at a 106 TCID50/mL dosage) and 100% (at 105 TCID50/mL) mortality rates were observed, while these rates were reduced to 56% and 68% in the ten-week-old groups, respectively. The mortality was significantly higher in the virus-exposed groups than in the control ones. In the sixteen-week-old group, 23% mortality was detected at a 105 TCID50/mL concentration of ECV. Here, a significant difference was not found between the exposed and control groups. The performed experiments show that different age groups of wels catfish may have various susceptibility to ECV. These findings draw attention to the importance of the prevention of/protection against virus infections in juvenile (up to 3-month-old) wels catfish in aquaculture. Full article
(This article belongs to the Special Issue Fish Virology)
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22 pages, 1977 KiB  
Article
Transcriptomic Analyses of Grapevine Leafroll-Associated Virus 3 Infection in Leaves and Berries of ‘Cabernet Franc’
by Yashu Song, Robert H. Hanner and Baozhong Meng
Viruses 2022, 14(8), 1831; https://doi.org/10.3390/v14081831 - 21 Aug 2022
Cited by 4 | Viewed by 1941
Abstract
Grapevine leafroll-associated virus 3 (GLRaV-3) is one of the most important viruses affecting global grape and wine production. GLRaV-3 is the chief agent associated with grapevine leafroll disease (GLRD), the most prevalent and economically destructive grapevine viral disease complex. Response of grapevine to [...] Read more.
Grapevine leafroll-associated virus 3 (GLRaV-3) is one of the most important viruses affecting global grape and wine production. GLRaV-3 is the chief agent associated with grapevine leafroll disease (GLRD), the most prevalent and economically destructive grapevine viral disease complex. Response of grapevine to GLRaV-3 infection at the gene expression level is poorly characterized, limiting the understanding of GLRaV-3 pathogenesis and viral-associated symptom development. In this research, we used RNA-Seq to profile the changes in global gene expression of Cabernet franc, a premium red wine grape, analyzing leaf and berry tissues at three key different developmental stages. We have identified 1457 differentially expressed genes (DEGs) in leaves and 1181 DEGs in berries. The expression profiles of a subset of DEGs were validated through RT-qPCR, including those involved in photosynthesis (VvPSBP1), carbohydrate partitioning (VvSUT2, VvHT5, VvGBSS1, and VvSUS), flavonoid biosynthesis (VvUFGT, VvLAR1, and VvFLS), defense response (VvPR-10.3, and VvPR-10.7), and mitochondrial activities (ETFB, TIM13, and NDUFA1). GLRaV-3 infection altered source–sink relationship between leaves and berries. Photosynthesis and photosynthate assimilation were inhibited in mature leaves while increased in young berries. The expression of genes involved in anthocyanin biosynthesis increased in GLRaV-3-infected leaves, correlating with interveinal tissue reddening, a hallmark of GLRD symptoms. Notably, we identified changes in gene expression that suggest a compromised sugar export and increased sugar retrieval in GLRaV-3-infected leaves. Genes associated with mitochondria were down-regulated in both leaves and berries of Cabernet franc infected with GLRaV-3. Results of the present study suggest that GLRaV-3 infection may disrupt mitochondrial function in grapevine leaves, leading to repressed sugar export and accumulation of sugar in mature leaf tissues. The excessive sugar accumulation in GLRaV-3-infected leaves may trigger downstream GLRD symptom development and negatively impact berry quality. We propose a working model to account for the molecular events underlying the pathogenesis of GLRaV-3 and symptom development. Full article
(This article belongs to the Special Issue A Tribute to Giovanni P. Martelli)
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26 pages, 6512 KiB  
Article
Induction of Systemic Resistance to Tobacco mosaic virus in Tomato through Foliar Application of Bacillus amyloliquefaciens Strain TBorg1 Culture Filtrate
by Ahmed Abdelkhalek, Dalia G. Aseel, Lóránt Király, András Künstler, Hassan Moawad and Abdulaziz A. Al-Askar
Viruses 2022, 14(8), 1830; https://doi.org/10.3390/v14081830 - 20 Aug 2022
Cited by 12 | Viewed by 2556
Abstract
The application of microbe-derived products as natural biocontrol agents to boost systemic disease resistance to virus infections in plants is a prospective strategy to make agriculture more sustainable and environmentally friendly. In the current study, the rhizobacterium Bacillus amyloliquefaciens strain TBorg1 was identified [...] Read more.
The application of microbe-derived products as natural biocontrol agents to boost systemic disease resistance to virus infections in plants is a prospective strategy to make agriculture more sustainable and environmentally friendly. In the current study, the rhizobacterium Bacillus amyloliquefaciens strain TBorg1 was identified based on 16S rRNA, rpoB, and gyrA gene sequences, and evaluated for its efficiency in conferring protection of tomato from infection by Tobacco mosaic virus (TMV). Under greenhouse circumstances, foliar sprays of TBorg1 culture filtrate (TBorg1-CF) promoted tomato growth, lowered disease severity, and significantly decreased TMV accumulation in systemically infected leaves of treated plants relative to untreated controls. TMV accumulation was reduced by 90% following the dual treatment, applied 24 h before and after TMV infection. Significant increases in levels of total soluble carbohydrates, proteins, and ascorbic acid were also found. In addition, a significant rise in activities of enzymes capable of scavenging reactive oxygen species (PPO and POX), as well as decreased levels of non-enzymatic oxidative stress markers (H2O2 and MDA) were observed, compared to untreated plants. Enhanced systemic resistance to TMV was indicated by significantly increased transcript accumulation of polyphenolic pathway (C4H, HCT, and CHI) and pathogenesis-related (PR-1 and PR-5) genes. Out of the 15 compounds identified in the GC-MS analysis, 1,2-benzenedicarboxylic acid mono(2-ethylhexyl) ester and phenol, 2,4-bis(1,1-dimethylethyl), as well as L-proline, N-valeryl-, and heptadecyl ester were present in the highest concentrations in the ethyl acetate extract of TBorg1-CF. In addition, significant amounts of n-hexadecanoic acid, pyrrolo [1,2-a] pyrazine-1,4-dione hexahydro-3-(2-methylpropyl)-, nonane, 5-butyl-, and eicosane were also detected. These compounds may act as inducers of systemic resistance to viral infection. Our findings indicate that the newly isolated B. amyloliquefaciens strain TBorg1 could be a potentially useful rhizobacterium for promoting plant growth and a possible source of biocontrol agents for combating plant virus infections. Full article
(This article belongs to the Section Viruses of Plants, Fungi and Protozoa)
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14 pages, 2433 KiB  
Article
Human Rhinoviruses in Pediatric Patients in a Tertiary Care Hospital in Germany: Molecular Epidemiology and Clinical Significance
by Franziska Neugebauer, Sandra Bergs, Uwe Gerd Liebert and Mario Hönemann
Viruses 2022, 14(8), 1829; https://doi.org/10.3390/v14081829 - 20 Aug 2022
Cited by 2 | Viewed by 1627
Abstract
Rhinoviruses (RVs) constitute a substantial public health burden. To evaluate their abundance and genetic diversity in pediatric patients, RV RNA in respiratory samples was assessed using real-time RT-PCR and partial nucleic acid sequencing of viral genomes. Additionally, clinical data were retrieved from patient [...] Read more.
Rhinoviruses (RVs) constitute a substantial public health burden. To evaluate their abundance and genetic diversity in pediatric patients, RV RNA in respiratory samples was assessed using real-time RT-PCR and partial nucleic acid sequencing of viral genomes. Additionally, clinical data were retrieved from patient charts to determine the clinical significance of pediatric RV infections. In total, the respiratory specimens of 776 patients (<18 years), collected from 2013 to 2017, were analyzed. Infections occurred throughout the entire year, with peaks occurring in fall and winter, and showed remarkably high intra- and interseasonal diversity for RV genotypes. RV species were detected in the following frequencies: 49.1% RV-A, 5.9% RV-B, and 43.6% RV-C. RV-C was found to be more frequently associated with asthma (p = 0.04) and bronchiolitis (p < 0.001), while RV-A was more frequently associated with fever (p = 0.001) and pneumonia (p = 0.002). Additionally, 35.3% of the patients had co-infections with other pathogens, which were associated with a longer hospital stay (p < 0.001), need for ventilation (p < 0.001), and pneumonia (p < 0.001). Taken together, this study shows pronounced RV genetic diversity in pediatric patients and indicates differences in RV-associated pathologies, as well as an important role for co-infections. Full article
(This article belongs to the Special Issue Rhinovirus Infections 2.0)
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12 pages, 3481 KiB  
Article
Self-Assembly of Porcine Parvovirus Virus-like Particles and Their Application in Serological Assay
by Yanfei Gao, Haiwei Wang, Shanghui Wang, Mingxia Sun, Zheng Fang, Xinran Liu, Xuehui Cai and Yabin Tu
Viruses 2022, 14(8), 1828; https://doi.org/10.3390/v14081828 - 20 Aug 2022
Viewed by 2107
Abstract
Porcine parvovirus (PPV) is widely prevalent in pig farms. PPV is closely related to porcine respiratory disease complex (PRDC) and porcine circovirus disease (PCVD), which seriously threatens the healthy development of the pig industry. Although commercial antibody detection kits are available, they are [...] Read more.
Porcine parvovirus (PPV) is widely prevalent in pig farms. PPV is closely related to porcine respiratory disease complex (PRDC) and porcine circovirus disease (PCVD), which seriously threatens the healthy development of the pig industry. Although commercial antibody detection kits are available, they are expensive and unsuitable for large-scale clinical practice. Here, a soluble VP2 protein of PPV is efficiently expressed in the E. coli expression system. The VP2 protein can be self-assembled into virus-like particles (VLPs) in vitro. After multiple steps of chromatography purification, PPV-VLPs with a purity of about 95% were obtained. An indirect, enzyme-linked immunosorbent assay (I-ELISA), comparable to a commercial PPV kit, was developed based on the purified PPV-VLPs and was used to detect 487 clinical pig serum samples. The results showed that the I-ELISA is a simple, cost-effective, and efficient method for the diagnosis of clinical pig serum and plasma samples. In summary, high-purity, tag-free PPV-VLPs were prepared, and the established VLP-based I-ELISA is of great significance for the sero-monitoring of antibodies against PPV. Full article
(This article belongs to the Special Issue Advances in Parvovirus Research 2022)
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20 pages, 4305 KiB  
Article
Pharmacophore-Model-Based Drug Repurposing for the Identification of the Potential Inhibitors Targeting the Allosteric Site in Dengue Virus NS5 RNA-Dependent RNA Polymerase
by Sanjay Kumar, Leena H. Bajrai, Arwa A. Faizo, Aiah M. Khateb, Areej A. Alkhaldy, Rashmi Rana, Esam I. Azhar and Vivek Dhar Dwivedi
Viruses 2022, 14(8), 1827; https://doi.org/10.3390/v14081827 - 20 Aug 2022
Cited by 8 | Viewed by 2706
Abstract
Dengue virus (DENV) is the causative agent of DENV infection. To tackle DENV infection, the development of therapeutic molecules as direct-acting antivirals (DAAs) has been demonstrated as a truly effective approach. Among various DENV drug targets, non-structural protein 5 (NS5)—a highly conserved protein [...] Read more.
Dengue virus (DENV) is the causative agent of DENV infection. To tackle DENV infection, the development of therapeutic molecules as direct-acting antivirals (DAAs) has been demonstrated as a truly effective approach. Among various DENV drug targets, non-structural protein 5 (NS5)—a highly conserved protein among the family Flaviviridae—carries the RNA-dependent RNA polymerase (DENVRdRp) domain at the C-terminal, and its “N-pocket” allosteric site is widely considered for anti-DENV drug development. Therefore, in this study, we developed a pharmacophore model by utilising 41 known inhibitors of the DENVRdRp domain, and performed model screening against the FDA’s approved drug database for drug repurposing against DENVRdRp. Herein, drugs complying with the pharmacophore hypothesis were further processed through standard-precision (SP) and extra-precision (XP) docking scores (DSs) and binding pose refinement based on MM/GBSA binding energy (BE) calculations. This resulted in the identification of four potential potent drugs: (i) desmopressin (DS: −10.52, BE: −69.77 kcal/mol), (ii) rutin (DS: −13.43, BE: −67.06 kcal/mol), (iii) lypressin (DS: −9.84, BE: −67.65 kcal/mol), and (iv) lanreotide (DS: −8.72, BE: −64.7 kcal/mol). The selected drugs exhibited relevant interactions with the allosteric N-pocket of DENVRdRp, including priming-loop and entry-point residues (i.e., R729, R737, K800, and E802). Furthermore, 100 ns explicit-solvent molecular dynamics simulations and end-point binding free energy assessments support the considerable stability and free energy of the selected drugs in the targeted allosteric pocket of DENVRdRp. Hence, these four drugs, repurposed as potent inhibitors of the allosteric site of DENVRdRp, are recommended for further validation using experimental assays. Full article
(This article belongs to the Section Viral Immunology, Vaccines, and Antivirals)
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11 pages, 3902 KiB  
Article
Complete Genome Analysis and Animal Model Development of Fowl Adenovirus 8b
by Aijing Liu, Yu Zhang, Jing Wang, Hongyu Cui, Xiaole Qi, Changjun Liu, Yanping Zhang, Kai Li, Li Gao, Xiaomei Wang, Yulong Gao and Qing Pan
Viruses 2022, 14(8), 1826; https://doi.org/10.3390/v14081826 - 20 Aug 2022
Cited by 2 | Viewed by 1667
Abstract
Inclusion body hepatitis (IBH), hydropericardium syndrome, and gizzard erosion associated with fowl adenovirus (FAdV) infection have caused notable economic losses worldwide. In 2020, severe IBH was observed in a layer chicken farm in Hebei Province, China. Liver samples were collected from layer chickens [...] Read more.
Inclusion body hepatitis (IBH), hydropericardium syndrome, and gizzard erosion associated with fowl adenovirus (FAdV) infection have caused notable economic losses worldwide. In 2020, severe IBH was observed in a layer chicken farm in Hebei Province, China. Liver samples were collected from layer chickens with severe IBH and virus isolation was performed in LMH cells. DNA sequence and bioinformatics analyses were conducted to determine the phylogenetic relationship and the pathogenicity assay was conducted in specific-pathogen-free (SPF) chickens. HeB20 strain was isolated and identified as FAdV-8b, and the complete genome was successfully sequenced (GenBank No. OK188966). Although widespread recombination in clinical strains has been reported within FAdVs, HeB20 showed some novel characteristics, and did not show any recombination, highlighting that recombinant and non-recombinant FAdV-8b coexist in the clinic poultry industry. Finally, pathogenicity animal model of HeB20 was developed and showed severe IBH and 10% mortality. Collectively, a new FAdV-8b strain (HeB20) was isolated and responsible for the severe IBH in layer chickens. Complete genome of HeB20 was sequenced and valuable for future epidemiological investigations. HeB20 was capable of inducing severe IBH and 10% mortality in SPF chickens; this animal model provides a powerful tool for the future vaccine development. Full article
(This article belongs to the Special Issue Avian Viral Immunosuppressive Disease)
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15 pages, 2196 KiB  
Article
Rotavirus C Replication in Porcine Intestinal Enteroids Reveals Roles for Cellular Cholesterol and Sialic Acids
by Yusheng Guo, Sergei Raev, Maryssa K. Kick, Molly Raque, Linda J. Saif and Anastasia N. Vlasova
Viruses 2022, 14(8), 1825; https://doi.org/10.3390/v14081825 - 20 Aug 2022
Cited by 5 | Viewed by 2111
Abstract
Rotaviruses (RVs) are a significant cause of severe diarrheal illness in infants and young animals, including pigs. Group C rotavirus (RVC) is an emerging pathogen increasingly reported in pigs and humans worldwide, and is currently recognized as the major cause of gastroenteritis in [...] Read more.
Rotaviruses (RVs) are a significant cause of severe diarrheal illness in infants and young animals, including pigs. Group C rotavirus (RVC) is an emerging pathogen increasingly reported in pigs and humans worldwide, and is currently recognized as the major cause of gastroenteritis in neonatal piglets that results in substantial economic losses to the pork industry. However, little is known about RVC pathogenesis due to the lack of a robust cell culture system, with the exception of the RVC Cowden strain. Here, we evaluated the permissiveness of porcine crypt-derived 3D and 2D intestinal enteroid (PIE) culture systems for RVC infection. Differentiated 3D and 2D PIEs were infected with porcine RVC (PRVC) Cowden G1P[1], PRVC104 G3P[18], and PRVC143 G6P[5] virulent strains, and the virus replication was measured by qRT-PCR. Our results demonstrated that all RVC strains replicated in 2D-PIEs poorly, while 3D-PIEs supported a higher level of replication, suggesting that RVC selectively infects terminally differentiated enterocytes, which were less abundant in the 2D vs. 3D PIE cultures. While cellular receptors for RVC are unknown, target cell surface carbohydrates, including histo-blood-group antigens (HBGAs) and sialic acids (SAs), are believed to play a role in cell attachment/entry. The evaluation of the selective binding of RVCs to different HBGAs revealed that PRVC Cowden G1P[1] replicated to the highest titers in the HBGA-A PIEs, while PRVC104 or PRVC143 achieved the highest titers in the HBGA-H PIEs. Further, contrasting outcomes were observed following sialidase treatment (resulting in terminal SA removal), which significantly enhanced Cowden and RVC143 replication, but inhibited the growth of PRVC104. These observations suggest that different RVC strains may recognize terminal (PRVC104) as well as internal (Cowden and RVC143) SAs on gangliosides. Finally, several cell culture additives, such as diethylaminoethyl (DEAE)-dextran, cholesterol, and bile extract, were tested to establish if they could enhance RVC replication. We observed that only DEAE-dextran significantly enhanced RVC attachment, but it had no effect on RVC replication. Additionally, the depletion of cellular cholesterol by MβCD inhibited Cowden replication, while the restoration of the cellular cholesterol partially reversed the MβCD effects. These results suggest that cellular cholesterol plays an important role in the replication of the PRVC strain tested. Overall, our study has established a novel robust and physiologically relevant system to investigate RVC pathogenesis. We also generated novel, experimentally derived evidence regarding the role of host glycans, DEAE, and cholesterol in RVC replication, which is critical for the development of control strategies. Full article
(This article belongs to the Section Animal Viruses)
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13 pages, 545 KiB  
Review
In Vivo and In Vitro Studies of Cigarette Smoke Effects on Innate Responses to Influenza Virus: A Matter of Models?
by Wenxin Wu, Jeremy S. Alexander and Jordan P. Metcalf
Viruses 2022, 14(8), 1824; https://doi.org/10.3390/v14081824 - 20 Aug 2022
Cited by 2 | Viewed by 2472
Abstract
Cigarette smoke (CS) is a significant public health problem and a leading risk factor for the development of chronic obstructive pulmonary disease (COPD) in the developed world. Respiratory viral infections, such as the influenza A virus (IAV), are associated with acute exacerbations of [...] Read more.
Cigarette smoke (CS) is a significant public health problem and a leading risk factor for the development of chronic obstructive pulmonary disease (COPD) in the developed world. Respiratory viral infections, such as the influenza A virus (IAV), are associated with acute exacerbations of COPD and are more severe in cigarette smokers. To fight against viral infection, the host has developed an innate immune system, which has complicated mechanisms regulating the expression and activation of cytokines and chemokines to maximize the innate and adaptive antiviral response, as well as limiting the immunopathology that leads to exaggerated lung damage. In the case of IAV, responders include airway and alveolar epithelia, lung macrophages and dendritic cells. To achieve a successful infection, IAV must overcome these defenses. In this review, we summarize the detrimental role of CS in influenza infections. This includes both immunosuppressive and proinflammatory effects on innate immune responses during IAV infection. Some of the results, with respect to CS effects in mouse models, appear to have discordant results, which could be at least partially addressed by standardization of animal viral infection models to evaluate the effect of CS exposure in this context. Full article
(This article belongs to the Special Issue Signaling Pathways in Viral Infection and Antiviral Immunity)
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12 pages, 688 KiB  
Article
CMV and EBV Co-Infection in HIV-Infected Children: Infection Rates and Analysis of Differential Expression of Cytokines in HIV Mono- and HIV–CMV–EBV Co-Infected Groups
by Fizza Nazim, Hammad Afzal Kayani, Apsara Ali Nathwani, Fatima Mir and Syed Hani Abidi
Viruses 2022, 14(8), 1823; https://doi.org/10.3390/v14081823 - 19 Aug 2022
Cited by 7 | Viewed by 2429
Abstract
(1) Background: CMV and EBV co-infections can affect the HIV disease progression by modulating the immune system. The disease dynamics can differ in HIV-positive adults and children. In Pakistan, HIV is rapidly expanding, especially in children; however, the prevalence of CMV and EBV [...] Read more.
(1) Background: CMV and EBV co-infections can affect the HIV disease progression by modulating the immune system. The disease dynamics can differ in HIV-positive adults and children. In Pakistan, HIV is rapidly expanding, especially in children; however, the prevalence of CMV and EBV co-infection and the effect on immune modulation in HIV-positive children are not known. This study aimed to bridge this gap by estimating the rate of active CMV and EBV co-infection in HIV-positive children, followed by the analysis of differential expression of cytokines in HIV mono- and HIV/CMV/EBV co-infected children. (2) Methods: DNA samples from 319 HIV-positive children, previously recruited as part of a study to investigate the HIV outbreak in Larkana, Pakistan, in 2019, were screened for CMV and EBV through qPCR. Subsequently, differences in HIV viral loads and CD4 counts were analyzed between the HIV mono- and HIV/CMV/EBV co-infected groups. The RNA samples were used to determine the differential expression of both pro- and anti-inflammatory cytokines in the mono- and co-infected groups using RT-qPCR, while unpaired T-test and Pearson correlation test were applied to, respectively, analyze the differential cytokine expression and correlation between cytokine in the two groups. (3) Results: Of 319 samples, the rate of active EBV and CMV co-infection in HIV-positive children was observed in 79.9% and 38.9%, respectively. A significant difference was observed in HIV viral load between HIV mono- and co-infected groups. IFN-γ expression was found to be lower in the HIV mono-infected group, while higher in all other three co-infected groups. Meanwhile, mRNA expression of TGF-β1 was found to be lower in HIV mono- and HIV–CMV–EBV co-infected groups, while higher in HIV–CMV and HIV–EBV co-infected groups. IFN-γ and IL-2 exhibited a significant positive correlation in all except HIV–CMV co-infected group. (4) Conclusions: The study suggests that the presence of EBV/CMV co-infection can affect the HIV viral loads and expression of certain cytokines (IFN-γ and TGF-β1), which may affect the HIV disease dynamics in infected children. Full article
(This article belongs to the Special Issue HIV and Co-infections: Updates and Insights)
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23 pages, 3180 KiB  
Article
A Systematic Review and Meta-Analysis of Serologic Response following Coronavirus Disease 2019 (COVID-19) Vaccination in Solid Organ Transplant Recipients
by Atsushi Sakuraba, Alexander Luna and Dejan Micic
Viruses 2022, 14(8), 1822; https://doi.org/10.3390/v14081822 - 19 Aug 2022
Cited by 24 | Viewed by 2955
Abstract
Solid organ transplant (SOT) recipients are at greater risk of coronavirus disease 2019 (COVID-19) and have attenuated response to vaccinations. In the present meta-analysis, we aimed to evaluate the serologic response to the COVID-19 vaccine in SOT recipients. A search of electronic databases [...] Read more.
Solid organ transplant (SOT) recipients are at greater risk of coronavirus disease 2019 (COVID-19) and have attenuated response to vaccinations. In the present meta-analysis, we aimed to evaluate the serologic response to the COVID-19 vaccine in SOT recipients. A search of electronic databases was conducted to identify SOT studies that reported the serologic response to COVID-19 vaccination. We analyzed 44 observational studies including 6158 SOT recipients. Most studies were on mRNA vaccination (mRNA-1273 or BNT162b2). After a single and two doses of vaccine, serologic response rates were 8.6% (95% CI 6.8–11.0) and 34.2% (95% CI 30.1–38.7), respectively. Compared to controls, response rates were lower after a single and two doses of vaccine (OR 0.0049 [95% CI 0.0021–0.012] and 0.0057 [95% CI 0.0030–0.011], respectively). A third dose improved the rate to 65.6% (95% CI 60.4–70.2), but in a subset of patients who had not achieved a response after two doses, it remained low at 35.7% (95% CI 21.2–53.3). In summary, only a small proportion of SOT recipients achieved serologic response to the COVID-19 mRNA vaccine, and that even the third dose had an insufficient response. Alternative strategies for prophylaxis in SOT patients need to be developed. Key Contribution: In this meta-analysis that included 6158 solid organ transplant recipients, the serologic response to the COVID-19 vaccine was extremely low after one (8.6%) and two doses (34.2%). The third dose of the vaccine improved the rate only to 66%, and in the subset of patients who had not achieved a response after two doses, it remained low at 36%. The results of our study suggest that a significant proportion of solid organ transplant recipients are unable to achieve a sufficient serologic response after completing not only the two series of vaccination but also the third booster dose. There is an urgent need to develop strategies for prophylaxis including modified vaccine schedules or the use of monoclonal antibodies in this vulnerable patient population. Full article
(This article belongs to the Special Issue SARS-CoV-2 and Other Vaccines: Immunogenicity Parameters and Protection)
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16 pages, 5922 KiB  
Article
Discovery and Characterization of a Novel Umbravirus from Paederia scandens Plants Showing Leaf Chlorosis and Yellowing Symptoms
by Lianshun Zheng, Shuai Fu, Yi Xie, Yang Han, Xueping Zhou and Jianxiang Wu
Viruses 2022, 14(8), 1821; https://doi.org/10.3390/v14081821 - 19 Aug 2022
Cited by 1 | Viewed by 1581
Abstract
Umbraviruses are a special class of plant viruses that do not encode any viral structural proteins. Here, a novel umbravirus that has been tentatively named Paederia scandens chlorosis yellow virus (PSCYV) was discovered through RNA-seq in Paederia scandens plants showing leaf chlorosis and [...] Read more.
Umbraviruses are a special class of plant viruses that do not encode any viral structural proteins. Here, a novel umbravirus that has been tentatively named Paederia scandens chlorosis yellow virus (PSCYV) was discovered through RNA-seq in Paederia scandens plants showing leaf chlorosis and yellowing symptoms. The PSCYV genome is a 4301 nt positive-sense, single strand RNA that contains four open reading frames (ORFs), i.e., ORF1–4, that encode P1–P4 proteins, respectively. Together, ORF1 and ORF2 are predicted to encode an additional protein, RdRp, through a −1 frameshift mechanism. The P3 protein encoded by ORF3 was predicted to be the viral long-distance movement protein. P4 was determined to function as the viral cell-to-cell movement protein (MP) and transcriptional gene silencing (TGS) suppressor. Both P1 and RdRp function as weak post-transcriptional gene silencing (PTGS) suppressors of PSCYV. The PVX-expression system indicated that all viral proteins may be symptom determinants of PSCYV. Phylogenetic analysis indicated that PSCYV is evolutionarily related to members of the genus Umbravirus in the family Tombusviridae. Furthermore, a cDNA infectious clone of PSCYV was successfully constructed and used to prove that PSCYV can infect both Paederia scandens and Nicotiana benthamiana plants through mechanical inoculation, causing leaf chlorosis and yellowing symptoms. These findings have broadened our understanding of umbraviruses and their host range. Full article
(This article belongs to the Special Issue Next-Generation Sequencing in Plant Virology)
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18 pages, 2339 KiB  
Article
Establishing an In Vitro System to Assess How Specific Antibodies Drive the Evolution of Foot-and-Mouth Disease Virus
by David J. King, Graham Freimanis, Chris Neil, Andrew Shaw, Tobias J. Tuthill, Emma Laing, Donald P. King and Lidia Lasecka-Dykes
Viruses 2022, 14(8), 1820; https://doi.org/10.3390/v14081820 - 19 Aug 2022
Cited by 3 | Viewed by 2189 | Correction
Abstract
Viruses can evolve to respond to immune pressures conferred by specific antibodies generated after vaccination and/or infection. In this study, an in vitro system was developed to investigate the impact of serum-neutralising antibodies upon the evolution of a foot-and-mouth disease virus (FMDV) isolate. [...] Read more.
Viruses can evolve to respond to immune pressures conferred by specific antibodies generated after vaccination and/or infection. In this study, an in vitro system was developed to investigate the impact of serum-neutralising antibodies upon the evolution of a foot-and-mouth disease virus (FMDV) isolate. The presence of sub-neutralising dilutions of specific antisera delayed the onset of virus-induced cytopathic effect (CPE) by up to 44 h compared to the untreated control cultures. Continued virus passage with sub-neutralising dilutions of these sera resulted in a decrease in time to complete CPE, suggesting that FMDV in these cultures adapted to escape immune pressure. These phenotypic changes were associated with three separate consensus-level non-synonymous mutations that accrued in the viral RNA-encoding amino acids at positions VP266, VP280 and VP1155, corresponding to known epitope sites. High-throughput sequencing also identified further nucleotide substitutions within the regions encoding the leader (Lpro), VP4, VP2 and VP3 proteins. While association of the later mutations with the adaptation to immune pressure must be further verified, these results highlight the multiple routes by which FMDV populations can escape neutralising antibodies and support the application of a simple in vitro approach to assess the impact of the humoral immune system on the evolution of FMDV and potentially other viruses. Full article
(This article belongs to the Special Issue Global Foot-and-Mouth Disease Control)
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10 pages, 2453 KiB  
Article
A TaqMan Probe-Based Multiplex Real-Time PCR for Simultaneous Detection of Porcine Epidemic Diarrhea Virus Subtypes G1 and G2, and Porcine Rotavirus Groups A and C
by Letian Zhang, Zhiwen Jiang, Zitong Zhou, Jiumeng Sun, Shiyu Yan, Wenting Gao, Yuekun Shao, Yuhe Bai, Yifan Wu, Zefei Yan, Shouzhi Sheng, Alexander Lai and Shuo Su
Viruses 2022, 14(8), 1819; https://doi.org/10.3390/v14081819 - 19 Aug 2022
Cited by 11 | Viewed by 2522
Abstract
Porcine viral diarrhea diseases affect the swine industry, resulting in significant economic losses. Porcine epidemic diarrhea virus (PEDV) genotypes G1 and G2, and groups A and C of the porcine rotavirus, are major etiological agents of severe gastroenteritis and profuse diarrhea, particularly among [...] Read more.
Porcine viral diarrhea diseases affect the swine industry, resulting in significant economic losses. Porcine epidemic diarrhea virus (PEDV) genotypes G1 and G2, and groups A and C of the porcine rotavirus, are major etiological agents of severe gastroenteritis and profuse diarrhea, particularly among piglets, with mortality rates of up to 100%. Based on the high prevalence rate and frequent co-infection of PEDV, RVA, and RVC, close monitoring is necessary to avoid greater economic losses. We have developed a multiplex TaqMan probe-based real-time PCR for the rapid simultaneous detection and differentiation of PEDV subtypes G1 and G2, RVA, and RVC. This test is highly sensitive, as the detection limits were 20 and 100 copies/μL for the G1 and G2 subtypes of PEDV, respectively, and 50 copies/μL for RVA and RVC, respectively. Eighty-eight swine clinical samples were used to evaluate this new test. The results were 100% in concordance with the standard methods. Since reassortment between porcine and human rotaviruses has been reported, this multiplex test not only provides a basis for the management of swine diarrheal viruses, but also has the potential to impact public health as well. Full article
(This article belongs to the Special Issue State-of-the-Art Porcine Virus Research in China)
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14 pages, 3814 KiB  
Article
Phenotypic and Genetic Studies of the Viral Lineage Associated with the Recent Yellow Fever Outbreak in Brazil
by Nathália Dias Furtado, Mariela Martínez Gómez, Iasmim Silva de Mello, Déberli Ruiz Fernandes and Myrna Cristina Bonaldo
Viruses 2022, 14(8), 1818; https://doi.org/10.3390/v14081818 - 19 Aug 2022
Cited by 1 | Viewed by 1364
Abstract
Yellow fever virus (YFV) caused an outbreak in the Brazilian Southeast from 2016 to 2019, of the most significant magnitude since the 1900s. An investigation of the circulating virus revealed that most of the genomes detected in this period carried nine unique amino [...] Read more.
Yellow fever virus (YFV) caused an outbreak in the Brazilian Southeast from 2016 to 2019, of the most significant magnitude since the 1900s. An investigation of the circulating virus revealed that most of the genomes detected in this period carried nine unique amino acid polymorphisms, with eight located in the non-structural proteins NS3 and NS5, which are pivotal for viral replication. To elucidate the effect of these amino acid changes on viral infection, we constructed viruses carrying amino acid alterations in NS3 and NS5, performed infection in different cells, and assessed their neurovirulence in BALB/c mice and infected AG129 mice. We observed that the residues that compose the YFV 2016–2019 molecular signature in the NS5 protein might have been related to an attenuated phenotype, and that the alterations in the NS3 protein only slightly affected viral infection in AG129 mice, increasing to a low extent the mortality rate of these animals. These results contributed to unveiling the role of specific naturally occurring amino acid changes in the circulating strain of YFV in Brazil. Full article
(This article belongs to the Special Issue Flaviviruses and Flavivirus Vaccines)
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10 pages, 2923 KiB  
Communication
Rapid Amplicon Nanopore Sequencing (RANS) for the Differential Diagnosis of Monkeypox Virus and Other Vesicle-Forming Pathogens
by Ofir Israeli, Yehoudit Guedj-Dana, Ohad Shifman, Shirley Lazar, Inbar Cohen-Gihon, Sharon Amit, Ronen Ben-Ami, Nir Paran, Ofir Schuster, Shay Weiss, Anat Zvi and Adi Beth-Din
Viruses 2022, 14(8), 1817; https://doi.org/10.3390/v14081817 - 18 Aug 2022
Cited by 10 | Viewed by 3200
Abstract
As of July 2022, more than 16,000 laboratory-confirmed monkeypox (MPX) cases have been reported worldwide. Until recently, MPX was a rare viral disease seldom detected outside Africa. MPX virus (MPXV) belongs to the Orthopoxvirus (OPV) genus and is a genetically close relative of [...] Read more.
As of July 2022, more than 16,000 laboratory-confirmed monkeypox (MPX) cases have been reported worldwide. Until recently, MPX was a rare viral disease seldom detected outside Africa. MPX virus (MPXV) belongs to the Orthopoxvirus (OPV) genus and is a genetically close relative of the Variola virus (the causative agent of smallpox). Following the eradication of smallpox, there was a significant decrease in smallpox-related morbidity and the population’s immunity to other OPV-related diseases such as MPX. In parallel, there was a need for differential diagnosis between the different OPVs’ clinical manifestations and diseases with similar symptoms (i.e., chickenpox, herpes simplex). The current study aimed to provide a rapid genetic-based diagnostic tool for accurate and specific identification of MPXV and additional related vesicle-forming pathogens. We initially assembled a list of 14 relevant viral pathogens, causing infectious diseases associated with vesicles, prone to be misdiagnosed as MPX. Next, we developed an approach that we termed rapid amplicon nanopore sequencing (RANS). The RANS approach uses diagnostic regions that harbor high homology in their boundaries and internal diagnostic SNPs that, when sequenced, aid the discrimination of each pathogen within a group. During a multiplex PCR amplification, a dA tail and a 5′-phosphonate were simultaneously added, thus making the PCR product ligation ready for nanopore sequencing. Following rapid sequencing (a few minutes), the reads were compared to a reference database and the nearest strain was identified. We first tested our approach using samples of known viruses cultured in cell lines. All the samples were identified correctly and swiftly. Next, we examined a variety of clinical samples from the 2022 MPX outbreak. Our RANS approach identified correctly all the PCR-positive MPXV samples and mapped them to strains that were sequenced during the 2022 outbreak. For the subset of samples that were negative for MPXV by PCR, we obtained definite results, identifying other vesicle-forming viruses: Human herpesvirus 3, Human herpesvirus 2, and Molluscum contagiosum virus. This work was a proof-of-concept study, demonstrating the potential of the RANS approach for rapid and discriminatory identification of a panel of closely related pathogens. The simplicity and affordability of our approach makes it straightforward to implement in any genetics lab. Moreover, other differential diagnostics panels might benefit from the implementation of the RANS approach into their diagnostics pipelines. Full article
(This article belongs to the Special Issue Monkeypox Virus (Mpox))
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19 pages, 17222 KiB  
Review
Stabilisation of Viral Membrane Fusion Proteins in Prefusion Conformation by Structure-Based Design for Structure Determination and Vaccine Development
by Henriette Ebel, Tim Benecke and Benjamin Vollmer
Viruses 2022, 14(8), 1816; https://doi.org/10.3390/v14081816 - 18 Aug 2022
Cited by 2 | Viewed by 2911
Abstract
The membrane surface of enveloped viruses contains dedicated proteins enabling the fusion of the viral with the host cell membrane. Working with these proteins is almost always challenging because they are membrane-embedded and naturally metastable. Fortunately, based on a range of different examples, [...] Read more.
The membrane surface of enveloped viruses contains dedicated proteins enabling the fusion of the viral with the host cell membrane. Working with these proteins is almost always challenging because they are membrane-embedded and naturally metastable. Fortunately, based on a range of different examples, researchers now have several possibilities to tame membrane fusion proteins, making them amenable for structure determination and immunogen generation. This review describes the structural and functional similarities of the different membrane fusion proteins and ways to exploit these features to stabilise them by targeted mutational approaches. The recent determination of two herpesvirus membrane fusion proteins in prefusion conformation holds the potential to apply similar methods to this group of viral fusogens. In addition to a better understanding of the herpesviral fusion mechanism, the structural insights gained will help to find ways to further stabilise these proteins using the methods described to obtain stable immunogens that will form the basis for the development of the next generation of vaccines and antiviral drugs. Full article
(This article belongs to the Special Issue Molecular Mechanism of Herpesvirus Entry)
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14 pages, 2458 KiB  
Article
Development of a Nucleocapsid Protein-Based Blocking ELISA for the Detection of Porcine Deltacoronavirus Antibodies
by Wenlong Wang, Yongning Zhang and Hanchun Yang
Viruses 2022, 14(8), 1815; https://doi.org/10.3390/v14081815 - 18 Aug 2022
Cited by 4 | Viewed by 1526
Abstract
Porcine deltacoronavirus (PDCoV) is an emerging enteropathogen which mainly causes diarrhea, dehydration and death in nursing piglets, threatening the global swine industry. Moreover, it can infect multiple animal species and humans. Hence, reliable diagnostic assays are needed to better control this zoonotic pathogen. [...] Read more.
Porcine deltacoronavirus (PDCoV) is an emerging enteropathogen which mainly causes diarrhea, dehydration and death in nursing piglets, threatening the global swine industry. Moreover, it can infect multiple animal species and humans. Hence, reliable diagnostic assays are needed to better control this zoonotic pathogen. Here, a blocking ELISA was developed using a recombinant nucleocapsid (N) protein as the coating antigen paired with an N-specific monoclonal antibody (mAb) as the detection antibody. The percent inhibition (PI) of the ELISA was determined using 384 swine serum samples, with an indirect immunofluorescence assay (IFA) as the reference method. Through receiver operating characteristic analysis in conjunction with Youden’s index, the optimal PI cut-off value was determined to be 51.65%, which corresponded to a diagnostic sensitivity of 98.79% and a diagnostic specificity of 100%. Of the 330 serum samples tested positive via IFA, 326 and 4 were tested positive and negative via the ELISA, respectively, while the 54 serum samples tested negative via IFA were all negative via the ELISA. The overall coincidence rate between the two assays was 98.96% (380/384). The ELISA exhibited good repeatability and did not cross-react with antisera against other swine pathogens. Overall, this is the first report on developing a blocking ELISA for PDCoV serodiagnosis. Full article
(This article belongs to the Special Issue State-of-the-Art Porcine Virus Research in China)
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11 pages, 2320 KiB  
Article
The Function behind the Relation between Lipid Metabolism and Vimentin on H9N2 Subtype AIV Replication
by Anran Lu, Jing Yang, Xiangyu Huang, Xinmei Huang, Guihu Yin, Yiqin Cai, Xiuli Feng, Xiaofei Zhang, Yin Li and Qingtao Liu
Viruses 2022, 14(8), 1814; https://doi.org/10.3390/v14081814 - 18 Aug 2022
Cited by 2 | Viewed by 2050
Abstract
Avian influenza caused by H9N2 subtype avian influenza virus (AIV) poses a great threat to the healthy development of the poultry industry. Vimentin is closely related to intracellular lipid metabolism, which plays an important role during the viral infection process. However, the function [...] Read more.
Avian influenza caused by H9N2 subtype avian influenza virus (AIV) poses a great threat to the healthy development of the poultry industry. Vimentin is closely related to intracellular lipid metabolism, which plays an important role during the viral infection process. However, the function of lipid metabolism and vimentin on H9N2 AIV replication is unclear. In this paper, the cholesterol level and 3-hydroxy-3-methylglutaryl coenzyme a reductase (HMGCR) phosphorylation were investigated in vimentin knockout (KO) and human cervical carcinoma cells (HeLa) cell with or without AIV infection. The results showed that compared to the control group without infected with H9N2 subtype AIV, the cholesterol contents were significantly increased, while HMGCR phosphorylation level was reduced in both KO and HeLa cell after virus infection. Furthermore, viral replication was significantly inhibited in the cells treated with the cholesterol inhibitor lovastatin. Compared with the control group, adenylate activated protein kinase (AMPK), a kinase regulating HMGCR enzymatic activity was inhibited in both KO and HeLa cells in the infected virus group, and AMPK phosphorylation levels were significantly lower in KO HeLa cell than that of HeLa cells. Additionally, after MβCD treatment, viral hemagglutinin (HA) gene level was significantly decreased in HeLa cells, while it was significantly increased in KO HeLa cells. In addition, vimentin expression was significantly increased in MβCD-treated HeLa cells with the viral infection and returned to normal levels after exogenous cholesterol to backfill the MβCD-treated cells. Therefore, the disruption of lipid rafts during the binding phase of viral invasion of cells significantly reduced viral infection. These studies indicated that the lipid rafts and cholesterol levels might be critical for H9N2 subtype AIV infection of human-derived cells and that vimentin might play an important role in the regulation of lipids on viral replication, which provided an important antiviral target against influenza virus. Full article
(This article belongs to the Section Animal Viruses)
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8 pages, 968 KiB  
Review
The Role of Immunometabolism in HIV-1 Pathogenicity: Links to Immune Cell Responses
by Eman Teer, Nyasha C. Mukonowenzou and M. Faadiel Essop
Viruses 2022, 14(8), 1813; https://doi.org/10.3390/v14081813 - 18 Aug 2022
Cited by 4 | Viewed by 2329
Abstract
With the successful roll-out of combination antiretroviral treatment, HIV is currently managed as a chronic illness. Of note, immune activation and chronic inflammation are hallmarks of HIV-1 infection that persists even though patients are receiving treatments. Despite strong evidence linking immune activation and [...] Read more.
With the successful roll-out of combination antiretroviral treatment, HIV is currently managed as a chronic illness. Of note, immune activation and chronic inflammation are hallmarks of HIV-1 infection that persists even though patients are receiving treatments. Despite strong evidence linking immune activation and low-grade inflammation to HIV-1 pathogenesis, the underlying mechanisms remain less well-understood. As intracellular metabolism is emerging as a crucial factor determining the fate and activity of immune cells, this review article focuses on how links between early immune responses and metabolic reprograming may contribute to HIV pathogenicity. Here, the collective data reveal that immunometabolism plays a key role in HIV-1 pathogenesis. For example, the shift from quiescent immune cells to its activation leads to perturbed metabolic circuits that are major drivers of immune cell dysfunction and an altered phenotype. These findings suggest that immunometabolic perturbations play a key role in the onset of non-AIDS-associated comorbidities and that they represent an attractive target to develop improved diagnostic tools and novel therapeutic strategies to help blunt HIV-1 pathogenesis. Full article
(This article belongs to the Special Issue HIV-1 Infection and Immunometabolism: Relevance to HIV Pathogenesis and Persistence)
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15 pages, 1377 KiB  
Article
The Predictive Role of Hepatitis B Biomarkers on HBV Reactivation following Direct-Acting Antiviral Therapy in HBV/HCV Coinfected Patients
by Chih-Wei Tseng, Wen-Chun Liu, Ping-Hung Ko, Yen-Chun Chen, Kuo-Chih Tseng and Ting-Tsung Chang
Viruses 2022, 14(8), 1812; https://doi.org/10.3390/v14081812 - 18 Aug 2022
Cited by 3 | Viewed by 1476
Abstract
Hepatitis B and C (HBV/HCV) coinfected patients have a potential risk of hepatitis B reactivation (HBVr) after direct-acting antivirals (DAAs) treatment. The study intends to investigate the predictive role of HBV biomarkers in HBVr. Forty-six HBV/HCV coinfected patients receiving DAAs were enrolled. All [...] Read more.
Hepatitis B and C (HBV/HCV) coinfected patients have a potential risk of hepatitis B reactivation (HBVr) after direct-acting antivirals (DAAs) treatment. The study intends to investigate the predictive role of HBV biomarkers in HBVr. Forty-six HBV/HCV coinfected patients receiving DAAs were enrolled. All patients completed treatment and follow-up to the 12th-week post-DAA treatment (P12). Blood samples were measured for HBV biomarkers, including hepatitis B surface antigen (HBsAg), hepatitis B core-related antigen (HBcrAg), and HBV pregenomic RNA (HBV pgRNA). The predictive factors for HBVr after DAA treatment were analyzed. Among 31 patients without nucleot(s)ide analogue (NA) treatment, seven (22.5%, 7/31) developed HBVr without hepatitis flare-up. Patients with HBVr had higher HBsAg titers than those without HBVr from baseline to P12 (p = 0.008, 0.009, 0.004, and 0.006 at baseline, week 4, end of treatment, and P12, respectively). The baseline HBsAg level was the only predictive factor associated with HBVr (HR, 2.303; 95% CI, 1.086–4.882; p = 0.030). In predicting HBVr, a baseline HBsAg titer > 20 IU/mL had a sensitivity, specificity, positive predictive value, and negative predictive value of 85.7%, 75.0%, 50%, and 94.7%, respectively. No patient had HBVr if the baseline HBsAg titer was <8 IU/mL. Serum HBcrAg and HBV pgRNA levels had no role in predicting HBVr. In conclusion, HBV/HCV coinfected patients are at risk of HBVr after DAA treatment. The baseline HBsAg level was the predictive factor associated with HBVr. Patients with a baseline HBsAg titer < 8 IU/mL can be considered as not having HBVr. Full article
(This article belongs to the Section Human Virology and Viral Diseases)
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14 pages, 5284 KiB  
Article
Characterization of the Intestinal Fungal Microbiome in HIV and HCV Mono-Infected or Co-Infected Patients
by Yue Yin, Maermaer Tuohutaerbieke, Chengjie Feng, Xinjie Li, Yuqi Zhang, Qiang Xu, Jing Tu, Ence Yang, Qinghua Zou and Tao Shen
Viruses 2022, 14(8), 1811; https://doi.org/10.3390/v14081811 - 18 Aug 2022
Cited by 5 | Viewed by 1405
Abstract
Intestinal mycobiome dysbiosis plays an important role in the advancement of HIV- and HCV-infected patients. Co-infection with HCV is an important risk factor for exacerbating immune activation in HIV-infected patients, and gut fungal microbial dysbiosis plays an important role. However, no systematic study [...] Read more.
Intestinal mycobiome dysbiosis plays an important role in the advancement of HIV- and HCV-infected patients. Co-infection with HCV is an important risk factor for exacerbating immune activation in HIV-infected patients, and gut fungal microbial dysbiosis plays an important role. However, no systematic study has been conducted on the intestinal fungal microbiome of HIV/HCV co-infected patients to date. Patients infected with HIV and HCV, either alone or in combination, and healthy volunteers were included. Stool samples were collected for fungal ITS sequencing and for further mycobiome statistical analysis. We found that the abundance of fungal species significantly decreased in the HIV/HCV co-infection group compared to in the healthy control group, while no significant differences were found in the mono-infection groups. Low-CD4 + T-cell patients in the HIV group and high-ALT-level patients in the HCV group were discovered to have a more chaotic fungal community. Furthermore, the opportunistic pathogenic fungal profiles and fungal inter-correlations in the co-infection group became less characteristic but more complicated than those in the mono-infection groups. Intestinal fungal dysregulation occurs in HIV- and HCV-infected patients, and this dysregulation is further complicated in HIV/HCV co-infected patients. Full article
(This article belongs to the Special Issue HIV and Co-infections: Updates and Insights)
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