Viruses

22 pages, 5646 KiB

Open AccessArticle

Epidemiological Features of Human Norovirus Genotypes before and after COVID-19 Countermeasures in Osaka, Japan

by Tatsuya Shirai, Juthamas Phadungsombat, Yumi Ushikai, Kunihito Yoshikaie, Tatsuo Shioda and Naomi Sakon

Viruses 2024, 16(4), 654; https://doi.org/10.3390/v16040654 - 22 Apr 2024

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Abstract

We investigated the molecular epidemiology of human norovirus (HuNoV) in all age groups using samples from April 2019 to March 2023, before and after the COVID-19 countermeasures were implemented. GII.2[P16] and GII.4[P31], the prevalent strains in Japan before COVID-19 countermeasures, remained prevalent during [...] Read more.

We investigated the molecular epidemiology of human norovirus (HuNoV) in all age groups using samples from April 2019 to March 2023, before and after the COVID-19 countermeasures were implemented. GII.2[P16] and GII.4[P31], the prevalent strains in Japan before COVID-19 countermeasures, remained prevalent during the COVID-19 pandemic, except from April to November 2020; in 2021, the prevalence of GII.2[P16] increased among children. Furthermore, there was an increase in the prevalence of GII.4[P16] after December 2022. Phylogenetic analysis of GII.P31 RdRp showed that some strains detected in 2022 belonged to a different cluster of other strains obtained during the present study period, suggesting that HuNoV strains will evolve differently even if they have the same type of RdRp. An analysis of the amino acid sequence of VP1 showed that some antigenic sites of GII.4[P16] were different from those of GII.4[P31]. The present study showed high infectivity of HuNoV despite the COVID-19 countermeasures and revealed changes in the prevalent genotypes and mutations of each genotype. In the future, we will investigate whether GII.4[P16] becomes more prevalent, providing new insights by comparing the new data with those analyzed in the present study. Full article

(This article belongs to the Special Issue Viral Genetic Variation)

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18 pages, 671 KiB

Open AccessArticle

Delving into the Aftermath of a Disease-Associated Near-Extinction Event: A Five-Year Study of a Serpentovirus (Nidovirus) in a Critically Endangered Turtle Population

by Kate Parrish, Peter Kirkland, Paul Horwood, Bruce Chessman, Shane Ruming, Gerry McGilvray, Karrie Rose, Jane Hall and Lee Skerratt

Viruses 2024, 16(4), 653; https://doi.org/10.3390/v16040653 - 22 Apr 2024

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Abstract

Bellinger River virus (BRV) is a serpentovirus (nidovirus) that was likely responsible for the catastrophic mortality of the Australian freshwater turtle Myuchelys georgesi in February 2015. From November 2015 to November 2020, swabs were collected from turtles during repeated river surveys to estimate [...] Read more.

Bellinger River virus (BRV) is a serpentovirus (nidovirus) that was likely responsible for the catastrophic mortality of the Australian freshwater turtle Myuchelys georgesi in February 2015. From November 2015 to November 2020, swabs were collected from turtles during repeated river surveys to estimate the prevalence of BRV RNA, identify risk factors associated with BRV infection, and refine sample collection. BRV RNA prevalence at first capture was significantly higher in M. georgesi (10.8%) than in a coexisting turtle, Emydura macquarii (1.0%). For M. georgesi, various risk factors were identified depending on the analysis method, but a positive BRV result was consistently associated with a larger body size. All turtles were asymptomatic when sampled and conjunctival swabs were inferred to be optimal for ongoing monitoring. Although the absence of disease and recent BRV detections suggests a reduced ongoing threat, the potential for the virus to persist in an endemic focus or resurge in cyclical epidemics cannot be excluded. Therefore, BRV is an ongoing potential threat to the conservation of M. georgesi, and strict adherence to biosecurity principles is essential to minimise the risk of reintroduction or spread of BRV or other pathogens. Full article

(This article belongs to the Special Issue Identifying and Characterizing Viral Infections in Reptiles, Amphibians, Fish and Other Aquatic Species)

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16 pages, 3486 KiB

Open AccessArticle

Heterologous Exchanges of Glycoprotein and Non-Virion Protein in Novirhabdoviruses: Assessment of Virulence in Yellow Perch (Perca flavescens) and Rainbow Trout (Oncorhynchus mykiss)

by Vikram N. Vakharia, Arun Ammayappan, Shamila Yusuff, Tarin M. Tesfaye and Gael Kurath

Viruses 2024, 16(4), 652; https://doi.org/10.3390/v16040652 - 22 Apr 2024

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Abstract

Infectious hematopoietic necrosis virus (IHNV) and viral hemorrhagic septicemia virus (VHSV) are rhabdoviruses in two different species belonging to the Novirhabdovirus genus. IHNV has a narrow host range restricted to trout and salmon species, and viruses in the M genogroup of IHNV have [...] Read more.

Infectious hematopoietic necrosis virus (IHNV) and viral hemorrhagic septicemia virus (VHSV) are rhabdoviruses in two different species belonging to the Novirhabdovirus genus. IHNV has a narrow host range restricted to trout and salmon species, and viruses in the M genogroup of IHNV have high virulence in rainbow trout (Oncorhynchus mykiss). In contrast, the VHSV genotype IVb that invaded the Great Lakes in the United States has a broad host range, with high virulence in yellow perch (Perca flavescens), but not in rainbow trout. By using reverse-genetic systems of IHNV-M and VHSV-IVb strains, we generated six IHNV:VHSV chimeric viruses in which the glycoprotein (G), non-virion-protein (NV), or both G and NV genes of IHNV-M were replaced with the analogous genes from VHSV-IVb, and vice versa. These chimeric viruses were used to challenge groups of rainbow trout and yellow perch. The parental recombinants rIHNV-M and rVHSV-IVb were highly virulent in rainbow trout and yellow perch, respectively. Parental rIHNV-M was avirulent in yellow perch, and chimeric rIHNV carrying G, NV, or G and NV genes from VHSV-IVb remained low in virulence in yellow perch. Similarly, the parental rVHSV-IVb exhibited low virulence in rainbow trout, and chimeric rVHSV with substituted G, NV, or G and NV genes from IHNV-M remained avirulent in rainbow trout. Thus, the G and NV genes of either virus were not sufficient to confer high host-specific virulence when exchanged into a heterologous species genome. Some exchanges of G and/or NV genes caused a loss of host-specific virulence, providing insights into possible roles in viral virulence or fitness, and interactions between viral proteins. Full article

(This article belongs to the Special Issue The World of Rhabdoviruses)

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26 pages, 451 KiB

Open AccessArticle

Why Certain Repurposed Drugs Are Unlikely to Be Effective Antivirals to Treat SARS-CoV-2 Infections

by Selwyn J. Hurwitz, Ramyani De, Julia C. LeCher, Jessica A. Downs-Bowen, Shu Ling Goh, Keivan Zandi, Tamara McBrayer, Franck Amblard, Dharmeshkumar Patel, James J. Kohler, Manoj Bhasin, Brian S. Dobosh, Vikas Sukhatme, Rabindra M. Tirouvanziam and Raymond F. Schinazi

Viruses 2024, 16(4), 651; https://doi.org/10.3390/v16040651 - 22 Apr 2024

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Abstract

Most repurposed drugs have proved ineffective for treating COVID-19. We evaluated median effective and toxic concentrations (EC₅₀, CC₅₀) of 49 drugs, mostly from previous clinical trials, in Vero cells. Ratios of reported unbound peak plasma concentrations, (C_max)/EC [...] Read more.

Most repurposed drugs have proved ineffective for treating COVID-19. We evaluated median effective and toxic concentrations (EC₅₀, CC₅₀) of 49 drugs, mostly from previous clinical trials, in Vero cells. Ratios of reported unbound peak plasma concentrations, (C_max)/EC₅₀, were used to predict the potential in vivo efficacy. The 20 drugs with the highest ratios were retested in human Calu-3 and Caco-2 cells, and their CC₅₀ was determined in an expanded panel of cell lines. Many of the 20 drugs with the highest ratios were inactive in human Calu-3 and Caco-2 cells. Antivirals effective in controlled clinical trials had unbound C_max/EC₅₀ ≥ 6.8 in Calu-3 or Caco-2 cells. EC₅₀ of nucleoside analogs were cell dependent. This approach and earlier availability of more relevant cultures could have reduced the number of unwarranted clinical trials. Full article

(This article belongs to the Special Issue Advances in Antiviral Agents against SARS-CoV-2 and Its Variants 2nd Edition)

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9 pages, 262 KiB

Open AccessCommunication

Association of the IFNG +874T/A Polymorphism with Symptomatic COVID-19 Susceptibility

by Kevin Matheus Lima de Sarges, Flávia Póvoa da Costa, Erika Ferreira dos Santos, Marcos Henrique Damasceno Cantanhede, Rosilene da Silva, Adriana de Oliveira Lameira Veríssimo, Maria de Nazaré do Socorro de Almeida Viana, Fabíola Brasil Barbosa Rodrigues, Mauro de Meira Leite, Maria Karoliny da Silva Torres, Christiane Bentes da Silva, Mioni Thieli Figueiredo Magalhães de Brito, Andréa Luciana Soares da Silva, Daniele Freitas Henriques, Izaura Maria Vieira Cayres Vallinoto, Giselle Maria Rachid Viana, Maria Alice Freitas Queiroz, Antonio Carlos Rosário Vallinoto and Eduardo José Melo dos Santos

Viruses 2024, 16(4), 650; https://doi.org/10.3390/v16040650 - 22 Apr 2024

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Abstract

Tumor necrosis factor (TNF) and interferon-gamma (IFNγ) are important inflammatory mediators in the development of cytokine storm syndrome (CSS). Single nucleotide polymorphisms (SNPs) regulate the expression of these cytokines, making host genetics a key factor in the prognosis of COVID-19. In this study, [...] Read more.

Tumor necrosis factor (TNF) and interferon-gamma (IFNγ) are important inflammatory mediators in the development of cytokine storm syndrome (CSS). Single nucleotide polymorphisms (SNPs) regulate the expression of these cytokines, making host genetics a key factor in the prognosis of COVID-19. In this study, we investigated the associations of the TNF -308G/A and IFNG +874T/A polymorphisms with COVID-19. We analyzed the frequencies of the two polymorphisms in the control groups (CG: TNF -308G/A, n = 497; IFNG +874T/A, n = 397), a group of patients with COVID-19 (CoV, n = 222) and among the subgroups of patients with nonsevere (n = 150) and severe (n = 72) COVID-19. We found no significant difference between the genotypic and allelic frequencies of TNF -308G/A in the groups analyzed; however, both the frequencies of the high expression genotype (TT) (CoV: 13.51% vs. CG: 6.30%; p = 0.003) and the *T allele (CoV: 33.56% vs. CG: 24. 81%; p = 0.001) of the IFNG +874T/A polymorphism were higher in the COVID-19 group than in the control group, with no differences between the subgroups of patients with nonsevere and severe COVID-19. The *T allele of IFNG +874T/A (rs2430561) is associated with susceptibility to symptomatic COVID-19. These SNPs provided valuables clues about the potential mechanism involved in the susceptibility to developing symptomatic COVID-19. Full article

(This article belongs to the Special Issue Basic Sciences for the Conquest of COVID-19)

13 pages, 4145 KiB

Open AccessArticle

Characterizing Infections in Two Epidemic Waves of SARS-CoV-2 Omicron Variants: A Cohort Study in Guangzhou, China

by Lin Qu, Chunyan Xie, Ming Qiu, Lina Yi, Zhe Liu, Lirong Zou, Pei Hu, Huimin Jiang, Huimin Lian, Mingda Yang, Haiyi Yang, Huiling Zeng, Huimin Chen, Jianguo Zhao, Jianpeng Xiao, Jianfeng He, Ying Yang, Liang Chen, Baisheng Li, Jiufeng Sun and Jing Lu Show full author list Hide full author list

Viruses 2024, 16(4), 649; https://doi.org/10.3390/v16040649 - 22 Apr 2024

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Abstract

Background: After the adjustment of COVID-19 epidemic policy, mainland China experienced two consecutive waves of Omicron variants within a seven-month period. In Guangzhou city, as one of the most populous regions, the viral infection characteristics, molecular epidemiology, and the dynamic of population immunity [...] Read more.

Background: After the adjustment of COVID-19 epidemic policy, mainland China experienced two consecutive waves of Omicron variants within a seven-month period. In Guangzhou city, as one of the most populous regions, the viral infection characteristics, molecular epidemiology, and the dynamic of population immunity are still elusive. Methods: We launched a prospective cohort study in the Guangdong Provincial CDC from December 2022 to July 2023. Fifty participants who received the same vaccination regimen and had no previous infection were recruited. Results: 90% of individuals were infected with Omicron BA.5* variants within three weeks in the first wave. Thirteen cases (28.26%) experienced infection with XBB.1* variants, occurring from 14 weeks to 21 weeks after the first wave. BA.5* infections exhibited higher viral loads in nasopharyngeal sites compared to oropharyngeal sites. Compared to BA.5* infections, the XBB.1* infections had significantly milder clinical symptoms, lower viral loads, and shorter durations of virus positivity. The infection with the BA.5* variant elicited varying levels of neutralizing antibodies against XBB.1* among different individuals, even with similar levels of BA.5* antibodies. The level of neutralizing antibodies specific to XBB.1* determined the risk of reinfection. Conclusions: The rapid large-scale infections of the Omicron variants have quickly established herd immunity among the population in mainland China. In the future of the COVID-19 epidemic, a lower infection rate but a longer duration can be expected. Given the large population size and ongoing diversified herd immunity, it remains crucial to closely monitor the molecular epidemiology of SARS-CoV-2 for the emergence of new variants of concern in this region. Additionally, the timely evaluation of the immune status across different age groups is essential for informing future vaccination strategies and intervention policies. Full article

(This article belongs to the Special Issue COVID-19 Diagnostics in Clinical Applications and Pandemic Controls 2024)

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14 pages, 873 KiB

Open AccessArticle

Sosuga Virus Detected in Egyptian Rousette Bats (Rousettus aegyptiacus) in Sierra Leone

by Brian R. Amman, Alusine H. Koroma, Amy J. Schuh, Immah Conteh, Tara K. Sealy, Ibrahim Foday, Jonathan Johnny, Ibrahim A. Bakarr, Shannon L. M. Whitmer, Emily A. Wright, Aiah A. Gbakima, James Graziano, Camilla Bangura, Emmanuel Kamanda, Augustus Osborne, Emmanuel Saidu, Jonathan A. Musa, Doris F. Bangura, Sammuel M. T. Williams, George M. Fefegula, Christian Sumaila, Juliet Jabaty, Fatmata H. James, Amara Jambai, Kate Garnett, Thomas F. Kamara, Jonathan S. Towner and Aiah Lebbie Show full author list Hide full author list

Viruses 2024, 16(4), 648; https://doi.org/10.3390/v16040648 - 22 Apr 2024

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Abstract

Sosuga virus (SOSV), a rare human pathogenic paramyxovirus, was first discovered in 2012 when a person became ill after working in South Sudan and Uganda. During an ecological investigation, several species of bats were sampled and tested for SOSV RNA and only one [...] Read more.

Sosuga virus (SOSV), a rare human pathogenic paramyxovirus, was first discovered in 2012 when a person became ill after working in South Sudan and Uganda. During an ecological investigation, several species of bats were sampled and tested for SOSV RNA and only one species, the Egyptian rousette bat (ERBs; Rousettus aegyptiacus), tested positive. Since that time, multiple other species have been sampled and ERBs in Uganda have continued to be the only species of bat positive for SOSV infection. Subsequent studies of ERBs with SOSV demonstrated that ERBs are a competent host for SOSV and shed this infectious virus while exhibiting only minor infection-associated pathology. Following the 2014 Ebola outbreak in West Africa, surveillance efforts focused on discovering reservoirs for zoonotic pathogens resulted in the capture and testing of many bat species. Here, SOSV RNA was detected by qRT-PCR only in ERBs captured in the Moyamba District of Sierra Leone in the central region of the country. These findings represent a substantial range extension from East Africa to West Africa for SOSV, suggesting that this paramyxovirus may occur in ERB populations throughout its sub-Saharan African range. Full article

(This article belongs to the Special Issue Bat- and Rodent-Borne Zoonotic Viruses)

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23 pages, 1257 KiB

Open AccessReview

Back to the Basics of SARS-CoV-2 Biochemistry: Microvascular Occlusive Glycan Bindings Govern Its Morbidities and Inform Therapeutic Responses

by David E. Scheim, Peter I. Parry, David J. Rabbolini, Colleen Aldous, Morimasa Yagisawa, Robert Clancy, Thomas J. Borody and Wendy E. Hoy

Viruses 2024, 16(4), 647; https://doi.org/10.3390/v16040647 - 22 Apr 2024

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Abstract

Consistent with the biochemistry of coronaviruses as well established over decades, SARS-CoV-2 makes its initial attachment to host cells through the binding of its spike protein (SP) to sialylated glycans (containing the monosaccharide sialic acid) on the cell surface. The virus can then [...] Read more.

Consistent with the biochemistry of coronaviruses as well established over decades, SARS-CoV-2 makes its initial attachment to host cells through the binding of its spike protein (SP) to sialylated glycans (containing the monosaccharide sialic acid) on the cell surface. The virus can then slide over and enter via ACE2. SARS-CoV-2 SP attaches particularly tightly to the trillions of red blood cells (RBCs), platelets and endothelial cells in the human body, each cell very densely coated with sialic acid surface molecules but having no ACE2 or minimal ACE2. These interlaced attachments trigger the blood cell aggregation, microvascular occlusion and vascular damage that underlie the hypoxia, blood clotting and related morbidities of severe COVID-19. Notably, the two human betacoronaviruses that express a sialic acid-cleaving enzyme are benign, while the other three—SARS, SARS-CoV-2 and MERS—are virulent. RBC aggregation experimentally induced in several animal species using an injected polysaccharide caused most of the same morbidities of severe COVID-19. This glycan biochemistry is key to disentangling controversies that have arisen over the efficacy of certain generic COVID-19 treatment agents and the safety of SP-based COVID-19 vaccines. More broadly, disregard for the active physiological role of RBCs yields unreliable or erroneous reporting of pharmacokinetic parameters as routinely obtained for most drugs and other bioactive agents using detection in plasma, with whole-blood levels being up to 30-fold higher. Appreciation of the active role of RBCs can elucidate the microvascular underpinnings of other health conditions, including cardiovascular disease, and therapeutic opportunities to address them. Full article

(This article belongs to the Special Issue Glycans in Virus-Host Interactions)

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15 pages, 3345 KiB

Open AccessArticle

PCV2 Induced Endothelial Derived IL-8 Affects MoDCs Maturation Mainly via NF-κB Signaling Pathway

by Mengyu Zhang, Weicheng Xu, Ning Yang, Zhuowei Li, Shuanghai Zhou, Xuewei Liu, Jianfang Wang and Huanrong Li

Viruses 2024, 16(4), 646; https://doi.org/10.3390/v16040646 - 22 Apr 2024

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Abstract

Porcine circovirus type 2 (PCV2) infection can cause immunosuppressive diseases in pigs. Vascular endothelial cells (VECs), as the target cells for PCV2, play an important role in the immune response and inflammatory regulation. Endothelial IL-8, which is produced by porcine hip artery endothelial [...] Read more.

Porcine circovirus type 2 (PCV2) infection can cause immunosuppressive diseases in pigs. Vascular endothelial cells (VECs), as the target cells for PCV2, play an important role in the immune response and inflammatory regulation. Endothelial IL-8, which is produced by porcine hip artery endothelial cells (PIECs) infected with PCV2, can inhibit the maturation of monocyte-derived dendritic cells (MoDCs). Here, we established a co-culture system of MoDCs and different groups of PIECs to further investigate the PCV2-induced endothelial IL-8 signaling pathway that drives the inhibition of MoDC maturation. The differentially expressed genes related to MoDC maturation were mainly enriched in the NF-κB and JAK2-STAT3 signaling pathways. Both the NF-κB related factor RELA and JAK2-STAT3 signaling pathway related factors (IL2RA, JAK, STAT2, STAT5, IL23A, IL7, etc.) decreased significantly in the IL-8 up-regulated group, and increased significantly in the down-regulated group. The expression of NF-κB p65 in the IL-8 up-regulated group was reduced significantly, and the expression of IκBα was increased significantly. Nuclear translocation of NF-κB p65 was inhibited, while the nuclear translocation of p-STAT3 was increased in MoDCs in the PCV2-induced endothelial IL-8 group. The results of treatment with NF-κB signaling pathway inhibitors showed that the maturation of MoDCs was inhibited and the expression of IL-12 and GM-CSF at mRNA level were lower. Inhibition of the JAK2-STAT3 signaling pathway had no significant effect on maturation, and the expression of IL-12 and GM-CSF at mRNA level produced no significant change. In summary, the NF-κB signaling pathway is the main signaling pathway of MoDC maturation, and is inhibited by the PCV2-induced up-regulation of endothelial-derived IL-8. Full article

(This article belongs to the Section Animal Viruses)

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18 pages, 2642 KiB

Open AccessArticle

Lysis Physiology of Pseudomonas aeruginosa Infected with ssRNA Phage PRR1

by Rimantas Daugelavičius, Greta Daujotaitė and Dennis H. Bamford

Viruses 2024, 16(4), 645; https://doi.org/10.3390/v16040645 - 21 Apr 2024

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Abstract

The phage PRR1 belongs to the Leviviridae family, a group of ssRNA bacteriophages that infect Gram-negative bacteria. The variety of host cells is determined by the specificity of PRR1 to a pilus encoded by a broad host range of IncP-type plasmids that confer [...] Read more.

The phage PRR1 belongs to the Leviviridae family, a group of ssRNA bacteriophages that infect Gram-negative bacteria. The variety of host cells is determined by the specificity of PRR1 to a pilus encoded by a broad host range of IncP-type plasmids that confer multiple types of antibiotic resistance to the host. Using P. aeruginosa strain PAO1 as a host, we analyzed the PRR1 infection cycle, focusing on cell lysis. PRR1 infection renders P. aeruginosa cells sensitive to lysozyme approximately 20 min before the start of a drop in suspension turbidity. At the same time, infected cells start to accumulate lipophilic anions. The on-line monitoring of the entire infection cycle showed that single-gene-mediated lysis strongly depends on the host cells’ physiological state. The blockage of respiration or a reduction in the intracellular ATP concentration during the infection resulted in the inhibition of lysis. The same effect was observed when the synthesis of PRR1 lysis protein was induced in an E. coli expression system. In addition, lysis was strongly dependent on the level of aeration. Dissolved oxygen concentrations sufficient to support cell growth did not ensure efficient lysis, and a coupling between cell lysis initiation and aeration level was observed. However, the duration of the drop in suspension turbidity did not depend on the level of aeration. Full article

(This article belongs to the Special Issue Phage Assembly Pathways — to the Memory of Lindsay Black 2.0)

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28 pages, 7343 KiB

Open AccessArticle

Accumulation Dynamics of Defective Genomes during Experimental Evolution of Two Betacoronaviruses

by Julia Hillung, María J. Olmo-Uceda, Juan C. Muñoz-Sánchez and Santiago F. Elena

Viruses 2024, 16(4), 644; https://doi.org/10.3390/v16040644 - 20 Apr 2024

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Abstract

Virus-encoded replicases often generate aberrant RNA genomes, known as defective viral genomes (DVGs). When co-infected with a helper virus providing necessary proteins, DVGs can multiply and spread. While DVGs depend on the helper virus for propagation, they can in some cases disrupt infectious [...] Read more.

Virus-encoded replicases often generate aberrant RNA genomes, known as defective viral genomes (DVGs). When co-infected with a helper virus providing necessary proteins, DVGs can multiply and spread. While DVGs depend on the helper virus for propagation, they can in some cases disrupt infectious virus replication, impact immune responses, and affect viral persistence or evolution. Understanding the dynamics of DVGs alongside standard viral genomes during infection remains unclear. To address this, we conducted a long-term experimental evolution of two betacoronaviruses, the human coronavirus OC43 (HCoV-OC43) and the murine hepatitis virus (MHV), in cell culture at both high and low multiplicities of infection (MOI). We then performed RNA-seq at regular time intervals, reconstructed DVGs, and analyzed their accumulation dynamics. Our findings indicate that DVGs evolved to exhibit greater diversity and abundance, with deletions and insertions being the most common types. Notably, some high MOI deletions showed very limited temporary existence, while others became prevalent over time. We observed differences in DVG abundance between high and low MOI conditions in HCoV-OC43 samples. The size distribution of HCoV-OC43 genomes with deletions differed between high and low MOI passages. In low MOI lineages, short and long DVGs were the most common, with an additional cluster in high MOI lineages which became more prevalent along evolutionary time. MHV also showed variations in DVG size distribution at different MOI conditions, though they were less pronounced compared to HCoV-OC43, suggesting a more random distribution of DVG sizes. We identified hotspot regions for deletions that evolved at a high MOI, primarily within cistrons encoding structural and accessory proteins. In conclusion, our study illustrates the widespread formation of DVGs during betacoronavirus evolution, influenced by MOI and cell- and virus-specific factors. Full article

(This article belongs to the Special Issue Viruses 2024 - A World of Viruses)

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25 pages, 3945 KiB

Open AccessArticle

Autophagy Deregulation in HIV-1-Infected Cells Increases Extracellular Vesicle Release and Contributes to TLR3 Activation

by Catherine DeMarino, Maria Cowen, Anastasia Williams, Pooja Khatkar, Fardokht A. Abulwerdi, Lisa Henderson, Julia Denniss, Michelle L. Pleet, Delores R. Luttrell, Iosif Vaisman, Lance A. Liotta, Joseph Steiner, Stuart F. J. Le Grice, Avindra Nath and Fatah Kashanchi

Viruses 2024, 16(4), 643; https://doi.org/10.3390/v16040643 - 20 Apr 2024

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Abstract

Human immunodeficiency virus type 1 (HIV-1) infection can result in HIV-associated neurocognitive disorder (HAND), a spectrum of disorders characterized by neurological impairment and chronic inflammation. Combined antiretroviral therapy (cART) has elicited a marked reduction in the number of individuals diagnosed with HAND. However, [...] Read more.

Human immunodeficiency virus type 1 (HIV-1) infection can result in HIV-associated neurocognitive disorder (HAND), a spectrum of disorders characterized by neurological impairment and chronic inflammation. Combined antiretroviral therapy (cART) has elicited a marked reduction in the number of individuals diagnosed with HAND. However, there is continual, low-level viral transcription due to the lack of a transcription inhibitor in cART regimens, which results in the accumulation of viral products within infected cells. To alleviate stress, infected cells can release accumulated products, such as TAR RNA, in extracellular vesicles (EVs), which can contribute to pathogenesis in neighboring cells. Here, we demonstrate that cART can contribute to autophagy deregulation in infected cells and increased EV release. The impact of EVs released from HIV-1 infected myeloid cells was found to contribute to CNS pathogenesis, potentially through EV-mediated TLR3 (Toll-like receptor 3) activation, suggesting the need for therapeutics to target this mechanism. Three HIV-1 TAR-binding compounds, 103FA, 111FA, and Ral HCl, were identified that recognize TAR RNA and reduce TLR activation. These data indicate that packaging of viral products into EVs, potentially exacerbated by antiretroviral therapeutics, may induce chronic inflammation of the CNS observed in cART-treated patients, and novel therapeutic strategies may be exploited to mitigate morbidity. Full article

(This article belongs to the Special Issue HIV-1 Infection and Immunometabolism: Relevance to HIV Pathogenesis and Persistence 2.0)

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10 pages, 570 KiB

Open AccessArticle

Monitoring HPV Prevalence and Risk Cofactors for Abnormal Cytology in the Post-Vaccination Period among Croatian Women

by Ena Pešut, Ivana Šimić, Rajko Fureš, Nina Milutin Gašperov, Cvjetko Lež, Fabijan Feratović, Tomica Kukina Žvigač, Magdalena Grce, Ivana Erceg Ivkošić and Ivan Sabol

Viruses 2024, 16(4), 642; https://doi.org/10.3390/v16040642 - 20 Apr 2024

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Abstract

The incidence and mortality rate of cervical cancer in Croatia remains a health challenge despite screening efforts. Besides the persistent infection with HPV, the development of cancer is also associated with some cofactors. The goal of this study was to assess circulating HPV [...] Read more.

The incidence and mortality rate of cervical cancer in Croatia remains a health challenge despite screening efforts. Besides the persistent infection with HPV, the development of cancer is also associated with some cofactors. The goal of this study was to assess circulating HPV genotypes and risk factors for the development of cervical precancer after almost 16 years from the onset of HPV vaccination in Croatia. In this study, a total of 321 women attending gynecological care were evaluated. Relevant medical and demographic information, including cytology, were collected. HPV genotyping was performed by PCR. Comparing the HPV types found in circulation in the pre-vaccination (1999–2015) and post-vaccination periods (2020–2023), a statistically significant reduction in HPV 31 was noted, while the overall prevalence increased in the post-vaccination period. Besides the expected HPV positivity as a risk factor, the history of smoking was associated with LSIL or worse cytology at enrollment. For the first time, this population study revealed a statistically significant shift in the HPV genotype in the post-vaccination period, as well as the confirmation of risk factors for the development of abnormal cytology among Croatian women. Full article

(This article belongs to the Special Issue Human and Animal Papillomavirus: Infections, Genetics, and Vaccines)

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13 pages, 3752 KiB

Open AccessArticle

New Genera and Species of Caulobacter and Brevundimonas Bacteriophages Provide Insights into Phage Genome Evolution

by Bert Ely, Michael Hils, Aaron Clarke, Maegan Albert, Nadia Holness, Jacob Lenski and Tannaz Mohammadi

Viruses 2024, 16(4), 641; https://doi.org/10.3390/v16040641 - 20 Apr 2024

Viewed by 378

Abstract

Previous studies have identified diverse bacteriophages that infect Caulobacter vibrioides strain CB15 ranging from small RNA phages to four genera of jumbo phages. In this study, we focus on 20 bacteriophages whose genomes range from 40 to 60 kb in length. Genome comparisons [...] Read more.

Previous studies have identified diverse bacteriophages that infect Caulobacter vibrioides strain CB15 ranging from small RNA phages to four genera of jumbo phages. In this study, we focus on 20 bacteriophages whose genomes range from 40 to 60 kb in length. Genome comparisons indicated that these diverse phages represent six Caulobacter phage genera and one additional genus that includes both Caulobacter and Brevundimonas phages. Within species, comparisons revealed that both single base changes and inserted or deleted genetic material cause the genomes of closely related phages to diverge. Among genera, the basic gene order and the orientation of key genes were retained with most of the observed variation occurring at ends of the genomes. We hypothesize that the nucleotide sequences of the ends of these phage genomes are less important than the need to maintain the size of the genome and the stability of the corresponding mRNAs. Full article

(This article belongs to the Special Issue Bacteriophage Diversity)

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21 pages, 7637 KiB

Open AccessArticle

The Dual-Targeted Fusion Inhibitor Clofazimine Binds to the S2 Segment of the SARS-CoV-2 Spike Protein

by Matthew R. Freidel, Pratiti A. Vakhariya, Shalinder K. Sardarni and Roger S. Armen

Viruses 2024, 16(4), 640; https://doi.org/10.3390/v16040640 - 20 Apr 2024

Viewed by 599

Abstract

Clofazimine and Arbidol have both been reported to be effective in vitro SARS-CoV-2 fusion inhibitors. Both are promising drugs that have been repurposed for the treatment of COVID-19 and have been used in several previous and ongoing clinical trials. Small-molecule bindings to expressed [...] Read more.

Clofazimine and Arbidol have both been reported to be effective in vitro SARS-CoV-2 fusion inhibitors. Both are promising drugs that have been repurposed for the treatment of COVID-19 and have been used in several previous and ongoing clinical trials. Small-molecule bindings to expressed constructs of the trimeric S2 segment of Spike and the full-length SARS-CoV-2 Spike protein were measured using a Surface Plasmon Resonance (SPR) binding assay. We demonstrate that Clofazimine, Toremifene, Arbidol and its derivatives bind to the S2 segment of the Spike protein. Clofazimine provided the most reliable and highest-quality SPR data for binding with S2 over the conditions explored. A molecular docking approach was used to identify the most favorable binding sites on the S2 segment in the prefusion conformation, highlighting two possible small-molecule binding sites for fusion inhibitors. Results related to molecular docking and modeling of the structure–activity relationship (SAR) of a newly reported series of Clofazimine derivatives support the proposed Clofazimine binding site on the S2 segment. When the proposed Clofazimine binding site is superimposed with other experimentally determined coronavirus structures in structure–sequence alignments, the changes in sequence and structure may rationalize the broad-spectrum antiviral activity of Clofazimine in closely related coronaviruses such as SARS-CoV, MERS, hCoV-229E, and hCoV-OC43. Full article

(This article belongs to the Special Issue Innovative Drug Discovery for Emerging Viral Diseases)

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13 pages, 402 KiB

Open AccessArticle

Vitamin D Levels and SARS-CoV-2 Infection among Medically Underserved Populations in the Minority and Rural Coronavirus Insights Study

by Makella S. Coudray, Shantoy Hansel, Salvatore Alesci, William A. Meyer III, Robert H. Christenson, Latrice G. Landry, Christina Edwards, Gary Puckrein, Derrick J. Forney and Ola Akinboboye

Viruses 2024, 16(4), 639; https://doi.org/10.3390/v16040639 - 19 Apr 2024

Viewed by 400

Abstract

Background: Extant literature presents contradictory findings on the role of vitamin D on SARS-CoV-2 infection. Our study included an examination of the relationship between vitamin D levels and SARS-CoV-2 infection among the Minority and Rural Coronavirus Insights Study (MRCIS) cohort, a diverse population [...] Read more.

Background: Extant literature presents contradictory findings on the role of vitamin D on SARS-CoV-2 infection. Our study included an examination of the relationship between vitamin D levels and SARS-CoV-2 infection among the Minority and Rural Coronavirus Insights Study (MRCIS) cohort, a diverse population of medically underserved persons presenting at five Federally qualified health centers in the United States. Methods: We conducted a descriptive analysis to explore the relationship between vitamin D levels and SARS-CoV-2 infection among medically underserved participants. A combined molecular and serologic assessment was used to determine the prevalence of SARS-CoV-2 infection. Vitamin D was examined as both a categorical (vitamin D status: deficient, insufficient, optimal) and continuous (vitamin D level) variable. Chi-squared testing, polynomial regression models, and logistic regression models were used to assess the relationship between vitamin D and SARS-CoV-2 infection. Results: The overall SARS-CoV-2 infection rate among participants was 25.9%. Most participants were either vitamin D deficient (46.5%) or insufficient (29.7%), and 23.8% had an optimal level. Vitamin D status was significantly associated with key SARS-CoV-2 infection risk factors. As mean vitamin D levels increased, the proportion of participants with SARS-CoV-2 infection decreased. For every 10 ng/mL increase in vitamin D levels the odds of SARS-CoV-2 infection decreased by 12% when adjusting for race/ethnicity and age (main effect model). Participants who identified as Hispanic/Latino or Black non-Hispanic had approximately two times increased odds of SARS-CoV-2 infection when adjusting for age and vitamin D levels compared to white non-Hispanics. However, when additional factors were added to the main effect model, the relationship between vitamin D levels and SARS-CoV-2 infection did not remain significant. Conclusion: Vitamin D levels were associated with an increased risk of SARS-CoV-2 infection. Hispanic/Latino and Black, non-Hispanic compared to White, non-Hispanic participants were at increased odds for infection, after adjusting for race/ethnicity and age. Full article

(This article belongs to the Special Issue Opportunistic Viral Infections 2nd Edition)

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7 pages, 211 KiB

Open AccessBrief Report

High-Pressure Processing of Different Tissue Homogenates from Pigs Challenged with the African Swine Fever Virus

by Stefano Petrini, Andrea Brutti, Cristina Casciari, Davide Calderone, Michela Pela, Monica Giammarioli, Cecilia Righi and Francesco Feliziani

Viruses 2024, 16(4), 638; https://doi.org/10.3390/v16040638 - 19 Apr 2024

Viewed by 287

Abstract

African swine fever (ASF) is a disease that is a growing threat to the global swine industry. Regulations and restrictions are placed on swine movement to limit the spread of the virus. However, these are costly and time-consuming. Therefore, this study aimed to [...] Read more.

African swine fever (ASF) is a disease that is a growing threat to the global swine industry. Regulations and restrictions are placed on swine movement to limit the spread of the virus. However, these are costly and time-consuming. Therefore, this study aimed to determine if high-pressure processing (HPP) sanitization techniques would be effective against the ASF virus. Here, it was hypothesized that HPP could inactivate or reduce ASF virus infectivity in tissue homogenates. To test this hypothesis, 30 aliquots of each homogenate (spleen, kidney, loin) were challenge-infected with the Turin/83 strain of ASF, at a 10 ^7.20 median hemadsorption dose (HAD)₅₀/mL. Subsequently, eight aliquots of each homogenate were treated with 600 millipascal (600 MPa) HPP for 3, 5, and 7 min. Six untreated aliquots were used as the controls. Virological results showed a reduction in the viral titer of more than 7-log. These results support the validity of the study hypothesis since HPP treatment was effective in inactivating ASFV in artificially prepared samples. Overall, this study suggests the need for further investigation of other ASFV-contaminated meat products. Full article

(This article belongs to the Section Animal Viruses)

16 pages, 5402 KiB

Open AccessArticle

Identification of New Microfoci and Genetic Characterization of Tick-Borne Encephalitis Virus Isolates from Eastern Germany and Western Poland

by Nina Król, Lidia Chitimia-Dobler, Gerhard Dobler, Dorota Kiewra, Aleksandra Czułowska, Anna Obiegala, Joanna Zajkowska, Thomas Juretzek and Martin Pfeffer

Viruses 2024, 16(4), 637; https://doi.org/10.3390/v16040637 - 19 Apr 2024

Viewed by 429

Abstract

(1) Background: Tick-borne encephalitis (TBE) is the most important tick-borne viral disease in Eurasia, although effective vaccines are available. Caused by the tick-borne encephalitis virus (TBEV, syn. Orthoflavivirus encephalitidis), in Europe, it is transmitted by ticks like Ixodes ricinus and Dermacentor reticulatus [...] Read more.

(1) Background: Tick-borne encephalitis (TBE) is the most important tick-borne viral disease in Eurasia, although effective vaccines are available. Caused by the tick-borne encephalitis virus (TBEV, syn. Orthoflavivirus encephalitidis), in Europe, it is transmitted by ticks like Ixodes ricinus and Dermacentor reticulatus. TBEV circulates in natural foci, making it endemic to specific regions, such as southern Germany and northeastern Poland. Our study aimed to identify new TBEV natural foci and genetically characterize strains in ticks in previously nonendemic areas in Eastern Germany and Western Poland. (2) Methods: Ticks were collected from vegetation in areas reported by TBE patients. After identification, ticks were tested for TBEV in pools of a maximum of 10 specimens using real-time RT-PCR. From the positive TBEV samples, E genes were sequenced. (3) Results: Among 8400 ticks from 19 sites, I. ricinus (n = 4784; 56.9%) was predominant, followed by D. reticulatus (n = 3506; 41.7%), Haemaphysalis concinna (n = 108; 1.3%), and I. frontalis (n = 2; <0.1%). TBEV was detected in 19 pools originating in six sites. The phylogenetic analyses revealed that TBEV strains from Germany and Poland clustered with other German strains, as well as those from Finland and Estonia. (4) Conclusions: Although there are still only a few cases are reported from these areas, people spending much time outdoors should consider TBE vaccination. Full article

(This article belongs to the Section Insect Viruses)

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11 pages, 1464 KiB

Open AccessArticle

U-CAN-seq: A Universal Competition Assay by Nanopore Sequencing

by Jennifer Diaz, John Sears, Che-Kang Chang, Jane Burdick, Isabella Law, Wes Sanders, Colton Linnertz, Paul Sylvester, Nathaniel Moorman, Martin T. Ferris and Mark T. Heise

Viruses 2024, 16(4), 636; https://doi.org/10.3390/v16040636 - 19 Apr 2024

Viewed by 382

Abstract

RNA viruses quickly evolve subtle genotypic changes that can have major impacts on viral fitness and host range, with potential consequences for human health. It is therefore important to understand the evolutionary fitness of novel viral variants relative to well-studied genotypes of epidemic [...] Read more.

RNA viruses quickly evolve subtle genotypic changes that can have major impacts on viral fitness and host range, with potential consequences for human health. It is therefore important to understand the evolutionary fitness of novel viral variants relative to well-studied genotypes of epidemic viruses. Competition assays are an effective and rigorous system with which to assess the relative fitness of viral genotypes. However, it is challenging to quickly and cheaply distinguish and quantify fitness differences between very similar viral genotypes. Here, we describe a protocol for using reverse transcription PCR in combination with commercial nanopore sequencing services to perform competition assays on untagged RNA viruses. Our assay, called the Universal Competition Assay by Nanopore Sequencing (U-CAN-seq), is relatively cheap and highly sensitive. We used a well-studied N24A mutation in the chikungunya virus (CHIKV) nsp3 gene to confirm that we could detect a competitive disadvantage using U-CAN-seq. We also used this approach to show that mutations to the CHIKV 5′ conserved sequence element that disrupt sequence but not structure did not affect the fitness of CHIKV. However, similar mutations to an adjacent CHIKV stem loop (SL3) did cause a fitness disadvantage compared to wild-type CHIKV, suggesting that structure-independent, primary sequence determinants in this loop play an important role in CHIKV biology. Our novel findings illustrate the utility of the U-CAN-seq competition assay. Full article

(This article belongs to the Section General Virology)

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22 pages, 3404 KiB

Open AccessArticle

Pathogenic and Apathogenic Strains of Lymphocytic Choriomeningitis Virus Have Distinct Entry and Innate Immune Activation Pathways

by Dylan M. Johnson, Nittaya Khakhum, Min Wang, Nikole L. Warner, Jenny D. Jokinen, Jason E. Comer and Igor S. Lukashevich

Viruses 2024, 16(4), 635; https://doi.org/10.3390/v16040635 - 19 Apr 2024

Viewed by 314

Abstract

Lymphocytic choriomeningitis virus (LCMV) and Lassa virus (LASV) share many genetic and biological features including subtle differences between pathogenic and apathogenic strains. Despite remarkable genetic similarity, the viscerotropic WE strain of LCMV causes a fatal LASV fever-like hepatitis in non-human primates (NHPs) while [...] Read more.

Lymphocytic choriomeningitis virus (LCMV) and Lassa virus (LASV) share many genetic and biological features including subtle differences between pathogenic and apathogenic strains. Despite remarkable genetic similarity, the viscerotropic WE strain of LCMV causes a fatal LASV fever-like hepatitis in non-human primates (NHPs) while the mouse-adapted Armstrong (ARM) strain of LCMV is deeply attenuated in NHPs and can vaccinate against LCMV-WE challenge. Here, we demonstrate that internalization of WE is more sensitive to the depletion of membrane cholesterol than ARM infection while ARM infection is more reliant on endosomal acidification. LCMV-ARM induces robust NF-κB and interferon response factor (IRF) activation while LCMV-WE seems to avoid early innate sensing and failed to induce strong NF-κB and IRF responses in dual-reporter monocyte and epithelial cells. Toll-like receptor 2 (TLR-2) signaling appears to play a critical role in NF-κB activation and the silencing of TLR-2 shuts down IL-6 production in ARM but not in WE-infected cells. Pathogenic LCMV-WE infection is poorly recognized in early endosomes and failed to induce TLR-2/Mal-dependent pro-inflammatory cytokines. Following infection, Interleukin-1 receptor-associated kinase 1 (IRAK-1) expression is diminished in LCMV-ARM- but not LCMV-WE-infected cells, which indicates it is likely involved in the LCMV-ARM NF-κB activation. By confocal microscopy, ARM and WE strains have similar intracellular trafficking although LCMV-ARM infection appears to coincide with greater co-localization of early endosome marker EEA1 with TLR-2. Both strains co-localize with Rab-7, a late endosome marker, but the interaction with LCMV-WE seems to be more prolonged. These findings suggest that LCMV-ARM’s intracellular trafficking pathway may facilitate interaction with innate immune sensors, which promotes the induction of effective innate and adaptive immune responses. Full article

(This article belongs to the Special Issue Arenaviruses 2024)

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12 pages, 4303 KiB

Open AccessArticle

SARS-CoV-2 Omicron BA.1 Variant Infection of Human Colon Epithelial Cells

by Avan Antia, David M. Alvarado, Qiru Zeng, Luis A. Casorla-Perez, Deanna L. Davis, Naomi M. Sonnek, Matthew A. Ciorba and Siyuan Ding

Viruses 2024, 16(4), 634; https://doi.org/10.3390/v16040634 - 19 Apr 2024

Viewed by 433

Abstract

The Omicron variant of SARS-CoV-2, characterized by multiple subvariants including BA.1, XBB.1.5, EG.5, and JN.1, became the predominant strain in early 2022. Studies indicate that Omicron replicates less efficiently in lung tissue compared to the ancestral strain. However, the infectivity of Omicron in [...] Read more.

The Omicron variant of SARS-CoV-2, characterized by multiple subvariants including BA.1, XBB.1.5, EG.5, and JN.1, became the predominant strain in early 2022. Studies indicate that Omicron replicates less efficiently in lung tissue compared to the ancestral strain. However, the infectivity of Omicron in the gastrointestinal tract is not fully defined, despite the fact that 70% of COVID-19 patients experience digestive disease symptoms. Here, using primary human colonoids, we found that, regardless of individual variability, Omicron infects colon cells similarly or less effectively than the ancestral strain or the Delta variant. The variant induced limited type III interferon expression and showed no significant impact on epithelial integrity. Further experiments revealed inefficient cell-to-cell spread and spike protein cleavage in the Omicron spike protein, possibly contributing to its lower infectious particle levels. The findings highlight the variant-specific replication differences in human colonoids, providing insights into the enteric tropism of Omicron and its relevance to long COVID symptoms. Full article

(This article belongs to the Special Issue Molecular Epidemiology of SARS-CoV-2: 2nd Edition)

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13 pages, 2321 KiB

Open AccessArticle

DMSO and Its Role in Differentiation Impact Efficacy of Human Adenovirus (HAdV) Infection in HepaRG Cells

by Katharina Hofmann, Samuel Hofmann, Franziska Weigl, Julia Mai and Sabrina Schreiner

Viruses 2024, 16(4), 633; https://doi.org/10.3390/v16040633 - 19 Apr 2024

Viewed by 450

Abstract

Differentiated HepaRG cells are popular in vitro cell models for hepatotoxicity studies. Their differentiation is usually supported by the addition of dimethyl sulfoxide (DMSO), an amphipathic solvent widely used in biomedicine, for example, in potential novel therapeutic drugs and cryopreservation of oocytes. Recent [...] Read more.

Differentiated HepaRG cells are popular in vitro cell models for hepatotoxicity studies. Their differentiation is usually supported by the addition of dimethyl sulfoxide (DMSO), an amphipathic solvent widely used in biomedicine, for example, in potential novel therapeutic drugs and cryopreservation of oocytes. Recent studies have demonstrated drastic effects, especially on epigenetics and extracellular matrix composition, induced by DMSO, making its postulated inert character doubtful. In this work, the influence of DMSO and DMSO-mediated modulation of differentiation on human adenovirus (HAdV) infection of HepaRG cells was investigated. We observed an increase in infectivity of HepaRG cells by HAdVs in the presence of 1% DMSO. However, this effect was dependent on the type of medium used for cell cultivation, as cells in William’s E medium showed significantly stronger effects compared with those cultivated in DMEM. Using different DMSO concentrations, we proved that the impact of DMSO on infectability was dose-dependent. Infection of cells with a replication-deficient HAdV type demonstrated that the mode of action of DMSO was based on viral entry rather than on viral replication. Taken together, these results highlight the strong influence of the used cell-culture medium on the performed experiments as well as the impact of DMSO on infectivity of HepaRG cells by HAdVs. As this solvent is widely used in cell culture, those effects must be considered, especially in screening of new antiviral compounds. Full article

(This article belongs to the Special Issue Research and Clinical Application of Adenovirus (AdV), Volume II)

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1 pages, 124 KiB

Open AccessCorrection

Correction: Hough et al. Fungal Viruses Unveiled: A Comprehensive Review of Mycoviruses. Viruses 2023, 15, 1202

by Bianca Hough, Emma Steenkamp, Brenda Wingfield and David Read

Viruses 2024, 16(4), 632; https://doi.org/10.3390/v16040632 - 19 Apr 2024

Viewed by 228

Abstract

In the original publication [...] Full article

(This article belongs to the Collection Mycoviruses)

15 pages, 3862 KiB

Open AccessArticle

Favipiravir Treatment Prolongs Survival in a Lethal BALB/c Mouse Model of Ebinur Lake Virus Infection

by Jingke Geng, Nanjie Ren, Cihan Yang, Fei Wang, Doudou Huang, Sergio Rodriguez, Zhiming Yuan and Han Xia

Viruses 2024, 16(4), 631; https://doi.org/10.3390/v16040631 - 18 Apr 2024

Viewed by 391

Abstract

Orthobunyavirus is the largest and most diverse genus in the family Peribunyaviridae. Orthobunyaviruses are widely distributed globally and pose threats to human and animal health. Ebinur Lake virus (EBIV) is a newly classified Orthobunyavirus detected in China, Russia, and Kenya. This study explored [...] Read more.

Orthobunyavirus is the largest and most diverse genus in the family Peribunyaviridae. Orthobunyaviruses are widely distributed globally and pose threats to human and animal health. Ebinur Lake virus (EBIV) is a newly classified Orthobunyavirus detected in China, Russia, and Kenya. This study explored the antiviral effects of two broad-spectrum antiviral drugs, favipiravir and ribavirin, in a BALB/c mouse model. Favipiravir significantly improved the clinical symptoms of infected mice, reduced viral titer and RNA copies in serum, and extended overall survival. The median survival times of mice in the vehicle- and favipiravir-treated groups were 5 and 7 days, respectively. Favipiravir significantly reduced virus titers 10- to 100-fold in sera at all three time points compared to vehicle-treated mice. And favipiravir treatment effectively reduced the virus copies by approximately 10-fold across the three time points, relative to vehicle-treated mice. The findings expand the antiviral spectrum of favipiravir for orthobunyaviruses in vivo. Full article

(This article belongs to the Special Issue Antivirals against Arboviruses)

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20 pages, 4429 KiB

Open AccessArticle

Identification of Bacteria and Viruses Associated with Patients with Acute Febrile Illness in Khon Kaen Province, Thailand

by Rungrat Jitvaropas, Vorthon Sawaswong, Yong Poovorawan, Nutthanun Auysawasdi, Viboonsak Vuthitanachot, Sirima Wongwairot, Wuttikon Rodkvamtook, Erica Lindroth, Sunchai Payungporn and Piyada Linsuwanon

Viruses 2024, 16(4), 630; https://doi.org/10.3390/v16040630 - 18 Apr 2024

Viewed by 436

Abstract

The majority of cases of undifferentiated acute febrile illness (AFI) in the tropics have an undefined etiology. In Thailand, AFI accounts for two-thirds of illnesses reported to the Ministry of Public Health. To characterize the bacterial and viral causes of these AFIs, we [...] Read more.

The majority of cases of undifferentiated acute febrile illness (AFI) in the tropics have an undefined etiology. In Thailand, AFI accounts for two-thirds of illnesses reported to the Ministry of Public Health. To characterize the bacterial and viral causes of these AFIs, we conducted molecular pathogen screening and serological analyses in patients who sought treatment in Chum Phae Hospital, Khon Kaen province, during the period from 2015 to 2016. Through integrated approaches, we successfully identified the etiology in 25.5% of cases, with dengue virus infection being the most common cause, noted in 17% of the study population, followed by scrub typhus in 3.8% and rickettsioses in 6.8%. Further investigations targeting viruses in patients revealed the presence of Guadeloupe mosquito virus (GMV) in four patients without other pathogen co-infections. The characterization of four complete genome sequences of GMV amplified from AFI patients showed a 93–97% nucleotide sequence identity with GMV previously reported in mosquitoes. Nucleotide substitutions resulted in amino acid differences between GMV amplified from AFI patients and mosquitoes, observed in 37 positions. However, these changes had undergone purifying selection pressure and potentially had a minimal impact on protein function. Our study suggests that the GMV strains identified in the AFI patients are relatively similar to those previously reported in mosquitoes, highlighting their potential role associated with febrile illness. Full article

(This article belongs to the Section Human Virology and Viral Diseases)

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17 pages, 818 KiB

Open AccessReview

Exploring Zika Virus Impact on Endothelial Permeability: Insights into Transcytosis Mechanisms and Vascular Leakage

by Dama Faniriantsoa Henrio Marcellin and Jufang Huang

Viruses 2024, 16(4), 629; https://doi.org/10.3390/v16040629 - 18 Apr 2024

Viewed by 534

Abstract

Treating brain disease is challenging, and the Zika virus (ZIKV) presents a unique obstacle due to its neuroinvasive nature. In this review, we discuss the immunopathogenesis of ZIKV and explore how the virus interacts with the body’s immune responses and the role of [...] Read more.

Treating brain disease is challenging, and the Zika virus (ZIKV) presents a unique obstacle due to its neuroinvasive nature. In this review, we discuss the immunopathogenesis of ZIKV and explore how the virus interacts with the body’s immune responses and the role of the protein Mfsd2a in maintaining the integrity of the blood–brain barrier (BBB) during ZIKV neuroinvasion. ZIKV has emerged as a significant public health concern due to its association with severe neurological problems, including microcephaly and Gillain–Barré Syndrome (GBS). Understanding its journey through the brain—particularly its interaction with the placenta and BBB—is crucial. The placenta, which is designed to protect the fetus, becomes a pathway for ZIKV when infected. The BBB is composed of brain endothelial cells, acts as a second barrier, and protects the fetal brain. However, ZIKV finds ways to disrupt these barriers, leading to potential damage. This study explores the mechanisms by which ZIKV enters the CNS and highlights the role of transcytosis, which allows the virus to move through the cells without significantly disrupting the BBB. Although the exact mechanisms of transcytosis are unclear, research suggests that ZIKV may utilize this pathway. Full article

(This article belongs to the Section Human Virology and Viral Diseases)

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12 pages, 244 KiB

Open AccessArticle

Dismantling Barriers to Hepatitis B and Delta Screening, Prevention, and Linkage to Care among the PWUD Community in Philadelphia

by Beatrice Zovich, Catherine Freeland, Holly Moore, Kara Sapp, Anousha Qureshi, Rachel Holbert, Jason Zambrano, Daljinder Bhangoo, Chari Cohen, Richard W. Hass and Amy Jessop

Viruses 2024, 16(4), 628; https://doi.org/10.3390/v16040628 - 18 Apr 2024

Viewed by 502

Abstract

The prevalence of hepatitis B and delta viruses (HBV/HDV) among people who use drugs (PWUD) remains largely unknown. In the context of one Philadelphia-based harm reduction organization (HRO), this study aimed to assess HBV/HDV prevalence and facilitate linkage to care. Participants completed a [...] Read more.

The prevalence of hepatitis B and delta viruses (HBV/HDV) among people who use drugs (PWUD) remains largely unknown. In the context of one Philadelphia-based harm reduction organization (HRO), this study aimed to assess HBV/HDV prevalence and facilitate linkage to care. Participants completed a demographic HBV/HDV risk factor survey and were screened for HBV and reflexively for HDV if positive for HBV surface antigen or isolated core antibody. Fisher’s exact tests and regression were used to understand relationships between risks and HBV blood markers. Of the 498 participants, 126 (25.3%) did not have hepatitis B immunity, 52.6% had been vaccinated against HBV, and 17.9% had recovered from a past infection. Eleven (2.2%) participants tested positive for isolated HBV core antibody, 10 (2.0%) for HBV surface antigen, and one (0.2%) for HDV antibody. History of incarceration was associated with current HBV infection, while transactional sex and experience of homelessness were predictive of previous exposure. This study found high rates of current and past HBV infection, and a 10% HBV/HDV co-infection rate. Despite availability of vaccine, one quarter of participants remained vulnerable to infection. Findings demonstrate the need to improve low-threshold HBV/HDV screening, vaccination, and linkage to care among PWUD. The study also identified gaps in the HBV/HDV care cascade, including lack of point-of-care diagnostics and lack of support for HROs to provide HBV services. Full article

(This article belongs to the Special Issue Cascade of Care for HIV and Hepatitis)

13 pages, 2287 KiB

Open AccessArticle

Trends in and Risk Factors for Drug Resistance in Mycobacterium tuberculosis in HIV-Infected Patients

by Xiaoqin Le, Xueqin Qian, Li Liu, Jianjun Sun, Wei Song, Tangkai Qi, Zhenyan Wang, Yang Tang, Shuibao Xu, Junyang Yang, Jiangrong Wang, Jun Chen, Renfang Zhang, Zhaoqin Zhu and Yinzhong Shen

Viruses 2024, 16(4), 627; https://doi.org/10.3390/v16040627 - 18 Apr 2024

Viewed by 359

Abstract

Trends in and risk factors for drug resistance in Mycobacterium tuberculosis (M. tuberculosis) in human immunodeficiency virus (HIV)-infected patients with active tuberculosis were analyzed. The clinical data of M. tuberculosis and HIV-coinfected patients treated at the Shanghai Public Health Clinical Center [...] Read more.

Trends in and risk factors for drug resistance in Mycobacterium tuberculosis (M. tuberculosis) in human immunodeficiency virus (HIV)-infected patients with active tuberculosis were analyzed. The clinical data of M. tuberculosis and HIV-coinfected patients treated at the Shanghai Public Health Clinical Center between 2010 and 2022 were collected. The diagnosis of tuberculosis was confirmed by solid or liquid culture. The phenotypic drug susceptibility test was carried out via the proportional method, and the resistance to first-line and second-line drugs was analyzed. Logistic regression analysis was performed to identify associated risk factors for drug resistance in M. tuberculosis. Of the 304 patients with a M. tuberculosis-positive culture and first-line drug susceptibility test results, 114 (37.5%) were resistant to at least one first-line anti-tuberculosis drug. Of the 93 patients with first-line and second-line drug susceptibility test results, 40 (43%) were resistant to at least one anti-tuberculosis drug, and 20 (21.5%), 27 (29.0%), 19 (20.4%), 16 (17.2%), and 14 (15.1%) were resistant to rifampicin, streptomycin, ofloxacin, levofloxacin, and moxifloxacin, respectively; 17 patients (18.3%) had multidrug-resistant tuberculosis (MDR-TB). Between 2010 and 2021, the rate of resistance to streptomycin and rifampicin ranged from 14.3% to 40.0% and from 8.0% to 26.3%, respectively, showing an increasing trend year by year. From 2016 to 2021, the rate of resistance to quinolones fluctuated between 7.7% and 27.8%, exhibiting an overall upward trend. Logistic regression analysis showed that being aged <60 years old was a risk factor for streptomycin resistance, mono-drug resistance, and any-drug resistance (RR 4.139, p = 0.023; RR 7.734, p = 0.047; RR 3.733, p = 0.009). Retreatment tuberculosis was a risk factor for resistance to rifampicin, ofloxacin, of levofloxacin (RR 2.984, p = 0.047; RR 4.517, p = 0.038; RR 6.277, p = 0.014). The drug resistance rates of M. tuberculosis to rifampicin and to quinolones in HIV/AIDS patients were high and have been increasing year by year. Age and a history of previous anti-tuberculosis treatment were the main factors associated with the development of drug resistance in HIV/AIDS patients with tuberculosis. Full article

(This article belongs to the Section Human Virology and Viral Diseases)

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17 pages, 802 KiB

Open AccessArticle

Detection and Characterization of Influenza A Virus Endemic Circulation in Suckling and Nursery Pigs Originating from Vaccinated Farms in the Same Production System

by Alessandra Silva Dias, Amy L. Vincent Baker, Rodney B. Baker, Jianqiang Zhang, Michael A. Zeller, Pravina Kitikoon and Phillip C. Gauger

Viruses 2024, 16(4), 626; https://doi.org/10.3390/v16040626 - 18 Apr 2024

Viewed by 493

Abstract

Inactivated influenza A virus (IAV) vaccines help reduce clinical disease in suckling piglets, although endemic infections still exist. The objective of this study was to evaluate the detection of IAV in suckling and nursery piglets from IAV-vaccinated sows from farms with endemic IAV [...] Read more.

Inactivated influenza A virus (IAV) vaccines help reduce clinical disease in suckling piglets, although endemic infections still exist. The objective of this study was to evaluate the detection of IAV in suckling and nursery piglets from IAV-vaccinated sows from farms with endemic IAV infections. Eight nasal swab collections were obtained from 135 two-week-old suckling piglets from four farms every other week from March to September 2013. Oral fluid samples were collected from the same group of nursery piglets. IAV RNA was detected in 1.64% and 31.01% of individual nasal swabs and oral fluids, respectively. H1N2 was detected most often, with sporadic detection of H1N1 and H3N2. Whole-genome sequences of IAV isolated from suckling piglets revealed an H1 hemagglutinin (HA) from the 1B.2.2.2 clade and N2 neuraminidase (NA) from the 2002A clade. The internal gene constellation of the endemic H1N2 was TTTTPT with a pandemic lineage matrix. The HA gene had 97.59% and 97.52% nucleotide and amino acid identities, respectively, to the H1 1B.2.2.2 used in the farm-specific vaccine. A similar H1 1B.2.2.2 was detected in the downstream nursery. These data demonstrate the low frequency of IAV detection in suckling piglets and downstream nurseries from farms with endemic infections in spite of using farm-specific IAV vaccines in sows. Full article

(This article belongs to the Special Issue Advances in Animal Influenza Virus Research: Third Edition)

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10 pages, 1728 KiB

Open AccessArticle

Spatial Transmission Characteristics of the Bluetongue Virus Serotype 3 Epidemic in The Netherlands, 2023

by Gert-Jan Boender, Thomas J. Hagenaars, Melle Holwerda, Marcel A. H. Spierenburg, Piet A. van Rijn, Arco N. van der Spek and Armin R. W. Elbers

Viruses 2024, 16(4), 625; https://doi.org/10.3390/v16040625 - 17 Apr 2024

Viewed by 628

Abstract

A devastating bluetongue (BT) epidemic caused by bluetongue virus serotype 3 (BTV-3) has spread throughout most of the Netherlands within two months since the first infection was officially confirmed in the beginning of September 2023. The epidemic comes with unusually strong suffering of [...] Read more.

A devastating bluetongue (BT) epidemic caused by bluetongue virus serotype 3 (BTV-3) has spread throughout most of the Netherlands within two months since the first infection was officially confirmed in the beginning of September 2023. The epidemic comes with unusually strong suffering of infected cattle through severe lameness, often resulting in mortality or euthanisation for welfare reasons. In total, tens of thousands of sheep have died or had to be euthanised. By October 2023, more than 2200 locations with ruminant livestock were officially identified to be infected with BTV-3, and additionally, ruminants from 1300 locations were showing BTV-associated clinical symptoms (but not laboratory-confirmed BT). Here, we report on the spatial spread and dynamics of this BT epidemic. More specifically, we characterized the distance-dependent intensity of the between-holding transmission by estimating the spatial transmission kernel and by comparing it to transmission kernels estimated earlier for BTV-8 transmission in Northwestern Europe in 2006 and 2007. The 2023 BTV-3 kernel parameters are in line with those of the transmission kernel estimated previously for the between-holding spread of BTV-8 in Europe in 2007. The 2023 BTV-3 transmission kernel has a long-distance spatial range (across tens of kilometres), evidencing that in addition to short-distance dispersal of infected midges, other transmission routes such as livestock transports probably played an important role. Full article

(This article belongs to the Special Issue Bluetongue, Epizootic Haemorrhagic Disease, and Other Emerging Orbiviruses)

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Viruses, Volume 16, Issue 4 (April 2024) – 170 articles

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