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Viruses
Volume 12
Issue 4
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Viruses, Volume 12, Issue 4 (April 2020) – 125 articles

Cover Story (view full-size image): The SARS-COV2 viral genome encodes at least 29 proteins that act as the basic functional building blocks. Structural knowledge of these proteins and the complexes they form to maintain viral functions provides critical information for understanding molecular mechanisms behind infection, forecasting evolutionary trajectories of the virus, and finding targets for new and repurposed antiviral drugs. Shown here is a modelled 3D map of the SARS-COV2 proteome consisting of the structural proteins (green), non-structural proteins, and their molecular interactions with each other and with the host targets (orange).View this paper
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11 pages, 1497 KiB  
Review
Microtubule Retrograde Motors and Their Role in Retroviral Transport
by Gianfranco Pietrantoni, Rodrigo Ibarra-Karmy and Gloria Arriagada
Viruses 2020, 12(4), 483; https://doi.org/10.3390/v12040483 - 24 Apr 2020
Cited by 6 | Viewed by 3475
Abstract
Following entry into the host cell, retroviruses generate a dsDNA copy of their genomes via reverse transcription, and this viral DNA is subsequently integrated into the chromosomal DNA of the host cell. Before integration can occur, however, retroviral DNA must be transported to [...] Read more.
Following entry into the host cell, retroviruses generate a dsDNA copy of their genomes via reverse transcription, and this viral DNA is subsequently integrated into the chromosomal DNA of the host cell. Before integration can occur, however, retroviral DNA must be transported to the nucleus as part of a ‘preintegration complex’ (PIC). Transporting the PIC through the crowded environment of the cytoplasm is challenging, and retroviruses have evolved different mechanisms to accomplish this feat. Within a eukaryotic cell, microtubules act as the roads, while the microtubule-associated proteins dynein and kinesin are the vehicles that viruses exploit to achieve retrograde and anterograde trafficking. This review will examine the various mechanisms retroviruses have evolved in order to achieve retrograde trafficking, confirming that each retrovirus has its own strategy to functionally subvert microtubule associated proteins. Full article
(This article belongs to the Special Issue Regulation and Exploitation of Microtubules by Viruses)
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15 pages, 4124 KiB  
Article
Mutation of Hydrophobic Residues in the C-Terminal Domain of the Marburg Virus Matrix Protein VP40 Disrupts Trafficking to the Plasma Membrane
by Kaveesha J. Wijesinghe, Luke McVeigh, Monica L. Husby, Nisha Bhattarai, Jia Ma, Bernard S. Gerstman, Prem P. Chapagain and Robert V. Stahelin
Viruses 2020, 12(4), 482; https://doi.org/10.3390/v12040482 - 24 Apr 2020
Cited by 6 | Viewed by 3504
Abstract
Marburg virus (MARV) is a lipid-enveloped negative sense single stranded RNA virus, which can cause a deadly hemorrhagic fever. MARV encodes seven proteins, including VP40 (mVP40), a matrix protein that interacts with the cytoplasmic leaflet of the host cell plasma membrane. VP40 traffics [...] Read more.
Marburg virus (MARV) is a lipid-enveloped negative sense single stranded RNA virus, which can cause a deadly hemorrhagic fever. MARV encodes seven proteins, including VP40 (mVP40), a matrix protein that interacts with the cytoplasmic leaflet of the host cell plasma membrane. VP40 traffics to the plasma membrane inner leaflet, where it assembles to facilitate the budding of viral particles. VP40 is a multifunctional protein that interacts with several host proteins and lipids to complete the viral replication cycle, but many of these host interactions remain unknown or are poorly characterized. In this study, we investigated the role of a hydrophobic loop region in the carboxy-terminal domain (CTD) of mVP40 that shares sequence similarity with the CTD of Ebola virus VP40 (eVP40). These conserved hydrophobic residues in eVP40 have been previously shown to be critical to plasma membrane localization and membrane insertion. An array of cellular experiments and confirmatory in vitro work strongly suggests proper orientation and hydrophobic residues (Phe281, Leu283, and Phe286) in the mVP40 CTD are critical to plasma membrane localization. In line with the different functions proposed for eVP40 and mVP40 CTD hydrophobic residues, molecular dynamics simulations demonstrate large flexibility of residues in the EBOV CTD whereas conserved mVP40 hydrophobic residues are more restricted in their flexibility. This study sheds further light on important amino acids and structural features in mVP40 required for its plasma membrane localization as well as differences in the functional role of CTD amino acids in eVP40 and mVP40. Full article
(This article belongs to the Special Issue The Role of Lipids in Virus Replication)
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18 pages, 4114 KiB  
Article
Comprehensive Analysis of HERV Transcriptome in HIV+ Cells: Absence of HML2 Activation and General Downregulation of Individual HERV Loci
by Nicole Grandi, Maria Paola Pisano, Sante Scognamiglio, Eleonora Pessiu and Enzo Tramontano
Viruses 2020, 12(4), 481; https://doi.org/10.3390/v12040481 - 23 Apr 2020
Cited by 9 | Viewed by 3767
Abstract
Human endogenous retrovirus (HERV) expression is currently studied for its possible activation by HIV infection. In this context, the HERV-K(HML2) group is the most investigated: it has been proposed that HIV-1 infection can prompt HML2 transcription, and that HML2 proteins can affect HIV-1 [...] Read more.
Human endogenous retrovirus (HERV) expression is currently studied for its possible activation by HIV infection. In this context, the HERV-K(HML2) group is the most investigated: it has been proposed that HIV-1 infection can prompt HML2 transcription, and that HML2 proteins can affect HIV-1 replication, either complementing HIV or possibly influencing antiretroviral therapy. However, little information is available on the expression of other HERV groups in HIV infection. In the present study, we used a bioinformatics pipeline to investigate the transcriptional modulation of approximately 3250 well-characterized HERV loci, comparing their expression in a public RNA-seq profile, including a HIV-1-infected and a control T cell culture. In our pilot study, we found approximately 200 HERV loci belonging to 35 HERV groups that were expressed in one or both conditions, with transcripts per million (TPM) values from 1 to >500. Intriguingly, HML2 elements constituted only the 3% of expressed HERV loci, and in most cases (160) HERV expression was downregulated in the HIV-infected culture, showing from a 1- to 14-fold decrease as compared to uninfected cells. HERV transcriptome has been inferred de novo and employed to predict a total of about 950 HERV open reading frames (ORFs). These have been validated according to the coding potential and estimated abundance of the corresponding transcripts, leading to a set of 57 putative proteins potentially encoded by 23 HERV loci. Analysis showed that some individual loci have a coding potential that deserves further investigation. Among them, a HML6 provirus at locus 19q13.43 was predicted to produce a transcript showing the highest TPM among HERV-derived transcripts, being upregulated in HIV+ cells and inferred to produce Gag and Env puteins with possible biological activity. Full article
(This article belongs to the Special Issue Antiretroviral Drug Development and HIV Cure Research)
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20 pages, 2314 KiB  
Article
Fc-Based Recombinant Henipavirus Vaccines Elicit Broad Neutralizing Antibody Responses in Mice
by Yaohui Li, Ruihua Li, Meirong Wang, Yujiao Liu, Ying Yin, Xiaodong Zai, Xiaohong Song, Yi Chen, Junjie Xu and Wei Chen
Viruses 2020, 12(4), 480; https://doi.org/10.3390/v12040480 - 23 Apr 2020
Cited by 12 | Viewed by 4745
Abstract
The genus Henipavirus (HNVs) includes two fatal viruses, namely Nipah virus (NiV) and Hendra virus (HeV). Since 1994, NiV and HeV have been endemic to the Asia–Pacific region and responsible for more than 600 cases of infections. Two emerging HNVs, Ghana virus (GhV) [...] Read more.
The genus Henipavirus (HNVs) includes two fatal viruses, namely Nipah virus (NiV) and Hendra virus (HeV). Since 1994, NiV and HeV have been endemic to the Asia–Pacific region and responsible for more than 600 cases of infections. Two emerging HNVs, Ghana virus (GhV) and Mojiang virus (MojV), are speculated to be associated with unrecognized human diseases in Africa and China, respectively. Despite many efforts to develop vaccines against henipaviral diseases, there is presently no licensed human vaccine. As HNVs are highly pathogenic and diverse, it is necessary to develop universal vaccines to prevent future outbreaks. The attachment enveloped glycoprotein (G protein) of HNVs mediates HNV attachment to the host cell’s surface receptors. G proteins have been used as a protective antigen in many vaccine candidates for HNVs. We performed quantitative studies on the antibody responses elicited by the G proteins of NiV, HeV, GhV, and MojV. We found that the G proteins of NiV and HeV elicited only a limited cross-reactive antibody response. Further, there was no cross-protection between MojV, GhV, and highly pathogenic HNVs. We then constructed a bivalent vaccine where the G proteins of NiV and HeV were fused with the human IgG1 Fc domain. The immunogenicity of the bivalent vaccine was compared with that of monovalent vaccines. Our results revealed that the Fc-based bivalent vaccine elicited a potent antibody response against both NiV and HeV. We also constructed a tetravalent Fc heterodimer fusion protein that contains the G protein domains of four HNVs. Immunization with the tetravalent vaccine elicited broad antibody responses against NiV, HeV, GhV, and MojV in mice, indicating compatibility among the four antigens in the Fc-fusion protein. These data suggest that our novel bivalent and tetravalent Fc-fusion proteins may be efficient candidates to prevent HNV infection. Full article
(This article belongs to the Section Viral Immunology, Vaccines, and Antivirals)
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8 pages, 1527 KiB  
Communication
Pantoea agglomerans-Infecting Bacteriophage vB_PagS_AAS21: A Cold-Adapted Virus Representing a Novel Genus within the Family Siphoviridae
by Monika Šimoliūnienė, Lidija Truncaitė, Emilija Petrauskaitė, Aurelija Zajančkauskaitė, Rolandas Meškys, Martynas Skapas, Algirdas Kaupinis, Mindaugas Valius and Eugenijus Šimoliūnas
Viruses 2020, 12(4), 479; https://doi.org/10.3390/v12040479 - 23 Apr 2020
Cited by 6 | Viewed by 3323
Abstract
A novel cold-adapted siphovirus, vB_PagS_AAS21 (AAS21), was isolated in Lithuania using Pantoea agglomerans as the host for phage propagation. AAS21 has an isometric head (~85 nm in diameter) and a non-contractile flexible tail (~174 × 10 nm). With a genome size of 116,649 [...] Read more.
A novel cold-adapted siphovirus, vB_PagS_AAS21 (AAS21), was isolated in Lithuania using Pantoea agglomerans as the host for phage propagation. AAS21 has an isometric head (~85 nm in diameter) and a non-contractile flexible tail (~174 × 10 nm). With a genome size of 116,649 bp, bacteriophage AAS21 is the largest Pantoea-infecting siphovirus sequenced to date. The genome of AAS21 has a G+C content of 39.0% and contains 213 putative protein-encoding genes and 29 genes for tRNAs. A comparative sequence analysis revealed that 89 AAS21 open reading frames (ORFs) code for unique proteins that have no reliable identity to database entries. In total, 63 AAS21 ORFs were functionally annotated, including those coding for the proteins responsible for virion morphogenesis, phage-host interactions, and DNA metabolism. Proteomic analysis led to the experimental identification of 19 virion proteins, including 11 that were predicted by bioinformatics approaches. Based on comparative phylogenetic analysis, AAS21 cannot be assigned to any genus currently recognized by ICTV and may represents a new branch of viruses within the family Siphoviridae. Full article
(This article belongs to the Section Bacterial Viruses)
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25 pages, 1137 KiB  
Article
Characterization of Potato Virus Y Isolates and Assessment of Nanopore Sequencing to Detect and Genotype Potato Viruses
by Michele Della Bartola, Stephen Byrne and Ewen Mullins
Viruses 2020, 12(4), 478; https://doi.org/10.3390/v12040478 - 23 Apr 2020
Cited by 46 | Viewed by 11524
Abstract
Potato virus Y (PVY) is the most economically important virus infecting cultivated potato (Solanum tuberosum L.). Accurate diagnosis is crucial to regulate the trade of tubers and for the sanitary selection of plant material for propagation. However, high genetic diversity of PVY [...] Read more.
Potato virus Y (PVY) is the most economically important virus infecting cultivated potato (Solanum tuberosum L.). Accurate diagnosis is crucial to regulate the trade of tubers and for the sanitary selection of plant material for propagation. However, high genetic diversity of PVY represents a challenge for the detection and classification of isolates. Here, the diversity of Irish PVY isolates from a germplasm collection and commercial sites was investigated using conventional molecular and serological techniques. Recombinant PVY isolates were prevalent, with PVYNTNa being the predominant genotype. In addition, we evaluated Nanopore sequencing to detect and reconstruct the whole genome sequence of four viruses (PVY, PVX, PVS, PLRV) and five PVY genotypes in a subset of eight potato plants. De novo assembly of Nanopore sequencing reads produced single contigs covering greater than 90% of the viral genome and sharing greater than 99.5% identity to the consensus sequences obtained with Illumina sequencing. Interestingly, single near full genome contigs were obtained for different isolates of PVY co-infecting the same plant. Mapping reads to available reference viral genomes enabled us to generate near complete genome sequences sharing greater than 99.90% identity to the Illumina-derived consensus. This is the first report describing the use of Oxford Nanopore’s MinION to detect and genotype potato viruses. We reconstructed the genome of PVY and other RNA viruses; indicating the technologies potential for virus detection in potato production systems, and for the study of genetic diversity of highly heterogeneous viruses such as PVY. Full article
(This article belongs to the Special Issue Plant Virus Pathogenesis and Disease Control)
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9 pages, 1496 KiB  
Article
Transport of Phage in Melon Plants and Inhibition of Progression of Bacterial Fruit Blotch
by Aryan Rahimi-Midani and Tae-Jin Choi
Viruses 2020, 12(4), 477; https://doi.org/10.3390/v12040477 - 23 Apr 2020
Cited by 12 | Viewed by 4021
Abstract
Bacterial fruit blotch (BFB) is an economically important disease in melons and watermelons for which no effective control method is available. Application of phytobacterium-infecting phage has been evaluated as an alternative means of preventing bacterial diseases in plants. Coating of seeds with bacteriophages [...] Read more.
Bacterial fruit blotch (BFB) is an economically important disease in melons and watermelons for which no effective control method is available. Application of phytobacterium-infecting phage has been evaluated as an alternative means of preventing bacterial diseases in plants. Coating of seeds with bacteriophages infecting Acidovorax citrulli, the causal agent of BFB, is effective for controlling the disease, as shown in our previous study. We evaluated the transport of bacteriophage ACPWH from soil to the leaves of melon plants, and we also evaluated its effect on BFB. Leaves of melon plants were spray-inoculated with A. citrulli, and bacteriophage ACPWH was added to soil after symptoms had developed. ACPWH was detected by PCR in foliar tissue 8 h after addition to soil. DAPI-stained ACPWH accumulated at the leaf tip after 24 h. Melon treated with ACPWH showed 27% disease severity, compared to 80% for the non-treated control, indicating that ACPWH can be used to control BFB. Full article
(This article belongs to the Special Issue Novel Concepts in Virology)
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4 pages, 4189 KiB  
Editorial
Shedding Light on the Effect of Natural Anti-Herpesvirus Alkaloids on SARS-CoV-2: A Treatment Option for COVID-19
by Sherif T. S. Hassan
Viruses 2020, 12(4), 476; https://doi.org/10.3390/v12040476 - 23 Apr 2020
Cited by 20 | Viewed by 5575
Abstract
The whole world is currently facing an unseen enemy, called coronavirus disease 2019 (COVID-19), which is causing a global pandemic. This disease is caused by a novel single-stranded enveloped RNA virus, known as the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Although huge efforts [...] Read more.
The whole world is currently facing an unseen enemy, called coronavirus disease 2019 (COVID-19), which is causing a global pandemic. This disease is caused by a novel single-stranded enveloped RNA virus, known as the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Although huge efforts are being made to produce effective therapies to combat this disease, it continues to be one of the greatest challenges in medicine. There is no doubt that herpesviruses are one of the most important viruses that infect humans and animals, and infections induced by these pathogens have developed into a great threat to public health. According to the currently available evidence, the correlation between herpesviruses and coronaviruses is limited to the induced complications following the infections. For instance, the inflammation that is induced at the sites of infection could tie these viruses to each other in a relationship. Another example, bovine herpesvirus 1, which is an important pathogen of cattle, can cause a severe respiratory infection; the same way in which SARS-CoV-2 affects humans. Considering the current circumstances related to the COVID-19 crisis, this editorial paper, which belongs to the Special Issue “Recent Advances in Herpesviruses Research: What’s in the Pipeline?” aims to draw attention to some natural anti-herpesvirus alkaloid compounds, which have recently been proven to have excellent inhibitory efficacy against SARS-CoV-2 replication. Thus, this special focus is an attempt to hunt down various treatment options to combat COVID-19 based on repurposing drugs that are known to have multiple antiviral properties, including against herpesvirus. Full article
(This article belongs to the Special Issue Recent Advances in Herpesviruses Research: What's in the Pipeline?)
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14 pages, 1577 KiB  
Article
HIV-1 Sub-Subtype A6: Settings for Normalised Identification and Molecular Epidemiology in the Southern Federal District, Russia
by Madita Schlösser, Vladimir V. Kartashev, Visa H. Mikkola, Andrey Shemshura, Sergey Saukhat, Dmitriy Kolpakov, Alexandr Suladze, Tatiana Tverdokhlebova, Katharina Hutt, Eva Heger, Elena Knops, Michael Böhm, Veronica Di Cristanziano, Rolf Kaiser, Anders Sönnerborg, Maurizio Zazzi, Marina Bobkova and Saleta Sierra
Viruses 2020, 12(4), 475; https://doi.org/10.3390/v12040475 - 22 Apr 2020
Cited by 19 | Viewed by 3566
Abstract
Russia has one of the largest and fastest growing HIV epidemics. However, epidemiological data are scarce. Sub-subtype A6 is most prevalent in Russia but its identification is challenging. We analysed protease/reverse transcriptase-, integrase-sequences, and epidemiological data from 303 patients to develop a methodology [...] Read more.
Russia has one of the largest and fastest growing HIV epidemics. However, epidemiological data are scarce. Sub-subtype A6 is most prevalent in Russia but its identification is challenging. We analysed protease/reverse transcriptase-, integrase-sequences, and epidemiological data from 303 patients to develop a methodology for the systematisation of A6 identification and to describe the HIV epidemiology in the Russian Southern Federal District. Drug consumption (32.0%) and heterosexual contact (27.1%) were the major reported transmission risks. This study successfully established the settings for systematic identification of A6 samples. Low frequency of subtype B (3.3%) and large prevalence of sub-subtype A6 (69.6%) and subtype G (23.4%) were detected. Transmitted PI- (8.8%) and NRTI-resistance (6.4%) were detected in therapy-naive patients. In therapy-experienced patients, 17.3% of the isolates showed resistance to PIs, 50.0% to NRTI, 39.2% to NNRTIs, and 9.5% to INSTIs. Multiresistance was identified in 52 isolates, 40 corresponding to two-class resistance and seven to three-class resistance. Two resistance-associated-mutations significantly associated to sub-subtype A6 samples: A62VRT and G190SRT. This study establishes the conditions for a systematic annotation of sub-subtype A6 to normalise epidemiological studies. Accurate knowledge on South Russian epidemiology will allow for the development of efficient regional frameworks for HIV-1 infection management. Full article
(This article belongs to the Section Animal Viruses)
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15 pages, 3064 KiB  
Article
Determination of Protein Interactions among Replication Components of Apple Necrotic Mosaic Virus
by Zhen-Lu Zhang, Fu-Jun Zhang, Peng-Fei Zheng, Yin-Huan Xie, Chun-Xiang You and Yu-Jin Hao
Viruses 2020, 12(4), 474; https://doi.org/10.3390/v12040474 - 22 Apr 2020
Cited by 3 | Viewed by 2482
Abstract
Apple mosaic disease is one of the most widely distributed and destructive diseases in apple cultivation worldwide, especially in China, whose apple yields account for more than 50% of the global total. Apple necrotic mosaic virus (ApNMV) is a newly identified ilarvirus that [...] Read more.
Apple mosaic disease is one of the most widely distributed and destructive diseases in apple cultivation worldwide, especially in China, whose apple yields account for more than 50% of the global total. Apple necrotic mosaic virus (ApNMV) is a newly identified ilarvirus that is closely associated with apple mosaic disease in China; however, basic viral protein interactions that play key roles in virus replication and the viral life cycle have not been determined in ApNMV. Here, we first identify an ApNMV–Lw isolate that belongs to subgroup 3 in the genus Ilarvirus. ApNMV–Lw was used to investigate interactions among viral components. ApNMV 1a and 2apol, encoded by RNA1 and RNA2, respectively, were co-localized in plant cell cytoplasm. ApNMV 1a interacted with itself at both the inter- and intramolecular levels, and its N-terminal portion played a key role in these interactions. 1a also interacted with 2apol, and 1a’s C-terminal, together with 2apol’s N-terminal, was required for this interaction. Moreover, the first 115 amino acids of 2apol were sufficient for permitting the 1a–2apol interaction. This study provides insight into the protein interactions among viral replication components of ApNMV, facilitating future investigations on its pathogenicity, as well as the development of strategies to control the virus and disease. Full article
(This article belongs to the Section Viruses of Plants, Fungi and Protozoa)
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15 pages, 2223 KiB  
Review
Broadly Neutralizing Bovine Antibodies: Highly Effective New Tools against Evasive Pathogens?
by Matthew J. Burke, Peter G. Stockley and Joan Boyes
Viruses 2020, 12(4), 473; https://doi.org/10.3390/v12040473 - 22 Apr 2020
Cited by 8 | Viewed by 5624
Abstract
Potent antibody-mediated neutralization is critical for an organism to combat the vast array of pathogens it will face during its lifetime. Due to the potential genetic diversity of some viruses, such as HIV-1 and influenza, standard neutralizing antibodies are often ineffective or easily [...] Read more.
Potent antibody-mediated neutralization is critical for an organism to combat the vast array of pathogens it will face during its lifetime. Due to the potential genetic diversity of some viruses, such as HIV-1 and influenza, standard neutralizing antibodies are often ineffective or easily evaded as their targets are masked or rapidly mutated. This has thwarted efforts to both prevent and treat HIV-1 infections and means that entirely new formulations are required to vaccinate against influenza each year. However, some rare antibodies isolated from infected individuals confer broad and potent neutralization. A subset of these broadly neutralizing antibodies possesses a long complementarity-determining 3 region of the immunoglobulin heavy chain (CDR H3). This feature generates unique antigen binding site configurations that can engage conserved but otherwise inaccessible epitope targets thus neutralizing many viral variants. Remarkably, ultralong CDR H3s are a common feature of the cow antibody repertoire and are encoded by a single variable, diversity, joining (VDJ) recombination that is extensively diversified prior to antigen exposure. Recently, it was shown that cows rapidly generate a broadly neutralizing response upon exposure to HIV-1 and this is primarily mediated by these novel ultralong antibody types. This review summarises the current knowledge of these unusual CDR H3 structures and discusses their known and potential future uses. Full article
(This article belongs to the Section Viral Immunology, Vaccines, and Antivirals)
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17 pages, 4557 KiB  
Review
RSV Reprograms the CDK9•BRD4 Chromatin Remodeling Complex to Couple Innate Inflammation to Airway Remodeling
by Allan R. Brasier
Viruses 2020, 12(4), 472; https://doi.org/10.3390/v12040472 - 22 Apr 2020
Cited by 18 | Viewed by 4931
Abstract
Respiratory syncytial virus infection is responsible for seasonal upper and lower respiratory tract infections worldwide, causing substantial morbidity. Self-inoculation of the virus into the nasopharynx results in epithelial replication and distal spread into the lower respiratory tract. Here, respiratory syncytial virus (RSV) activates [...] Read more.
Respiratory syncytial virus infection is responsible for seasonal upper and lower respiratory tract infections worldwide, causing substantial morbidity. Self-inoculation of the virus into the nasopharynx results in epithelial replication and distal spread into the lower respiratory tract. Here, respiratory syncytial virus (RSV) activates sentinel cells important in the host inflammatory response, resulting in epithelial-derived cytokine and interferon (IFN) expression resulting in neutrophilia, whose intensity is associated with disease severity. I will synthesize key findings describing how RSV replication activates intracellular NFκB and IRF signaling cascades controlling the innate immune response (IIR). Recent studies have implicated a central role for Scg1a1+ expressing progenitor cells in IIR, a cell type uniquely primed to induce neutrophilic-, T helper 2 (Th2)-polarizing-, and fibrogenic cytokines that play distinct roles in disease pathogenesis. Molecular studies have linked the positive transcriptional elongation factor-b (P-TEFb), a pleiotrophic chromatin remodeling complex in immediate-early IIR gene expression. Through intrinsic kinase activity of cyclin dependent kinase (CDK) 9 and atypical histone acetyl transferase activity of bromodomain containing protein 4 (BRD4), P-TEFb mediates transcriptional elongation of IIR genes. Unbiased proteomic studies show that the CDK9•BRD4 complex is dynamically reconfigured by the innate response and targets TGFβ-dependent fibrogenic gene networks. Chronic activation of CDK9•BRD4 mediates chromatin remodeling fibrogenic gene networks that cause epithelial mesenchymal transition (EMT). Mesenchymal transitioned epithelial cells elaborate TGFβ and IL6 that function in a paracrine manner to expand the population of subepithelial myofibroblasts. These findings may account for the long-term reduction in pulmonary function in children with severe lower respiratory tract infection (LRTI). Modifying chromatin remodeling properties of the CDK9•BRD4 coactivators may provide a mechanism for reducing post-infectious airway remodeling that are a consequence of severe RSV LRTIs. Full article
(This article belongs to the Special Issue From RSV to hMPV: Role of Innate Immunity in Pathogenesis)
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25 pages, 1163 KiB  
Review
Role of Divalent Cations in HIV-1 Replication and Pathogenicity
by Nabab Khan, Xuesong Chen and Jonathan D. Geiger
Viruses 2020, 12(4), 471; https://doi.org/10.3390/v12040471 - 21 Apr 2020
Cited by 15 | Viewed by 4064
Abstract
Divalent cations are essential for life and are fundamentally important coordinators of cellular metabolism, cell growth, host-pathogen interactions, and cell death. Specifically, for human immunodeficiency virus type-1 (HIV-1), divalent cations are required for interactions between viral and host factors that govern HIV-1 replication [...] Read more.
Divalent cations are essential for life and are fundamentally important coordinators of cellular metabolism, cell growth, host-pathogen interactions, and cell death. Specifically, for human immunodeficiency virus type-1 (HIV-1), divalent cations are required for interactions between viral and host factors that govern HIV-1 replication and pathogenicity. Homeostatic regulation of divalent cations’ levels and actions appear to change as HIV-1 infection progresses and as changes occur between HIV-1 and the host. In people living with HIV-1, dietary supplementation with divalent cations may increase HIV-1 replication, whereas cation chelation may suppress HIV-1 replication and decrease disease progression. Here, we review literature on the roles of zinc (Zn2+), iron (Fe2+), manganese (Mn2+), magnesium (Mg2+), selenium (Se2+), and copper (Cu2+) in HIV-1 replication and pathogenicity, as well as evidence that divalent cation levels and actions may be targeted therapeutically in people living with HIV-1. Full article
(This article belongs to the Special Issue HIV-1 Transcription Regulation)
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14 pages, 6994 KiB  
Article
Experimental Infection Using Mouse-Adapted Influenza B Virus in a Mouse Model
by Elena Prokopyeva, Olga Kurskaya, Ivan Sobolev, Mariia Solomatina, Tatyana Murashkina, Anastasia Suvorova, Alexander Alekseev, Daria Danilenko, Andrey Komissarov, Artem Fadeev, Edward Ramsay, Alexander Shestopalov, Alexander Dygai and Kirill Sharshov
Viruses 2020, 12(4), 470; https://doi.org/10.3390/v12040470 - 21 Apr 2020
Cited by 6 | Viewed by 3487
Abstract
Every year, influenza B viruses (IBVs) contribute to annual illness, and infection can lead to serious respiratory disease among humans. More attention is needed in several areas, such as increasing virulence or pathogenicity of circulating B viruses and developing vaccines against current influenza. [...] Read more.
Every year, influenza B viruses (IBVs) contribute to annual illness, and infection can lead to serious respiratory disease among humans. More attention is needed in several areas, such as increasing virulence or pathogenicity of circulating B viruses and developing vaccines against current influenza. Since preclinical trials of anti-influenza drugs are mainly conducted in mice, we developed an appropriate infection model, using an antigenically-relevant IBV strain, for furtherance of anti-influenza drug testing and influenza vaccine protective efficacy analysis. A Victoria lineage (clade 1A) IBV was serially passaged 17 times in BALB/c mice, and adaptive amino acid substitutions were found in hemagglutinin (HA) (T214I) and neuraminidase (NA) (D432N). By electron microscopy, spherical and elliptical IBV forms were noted. Light microscopy showed that mouse-adapted IBVs caused influenza pneumonia on day 6 post inoculation. We evaluated the illness pathogenicity, viral load, and histopathological features of mouse-adapted IBVs and estimated anti-influenza drugs and vaccine efficiency in vitro and in vivo. Assessment of an investigational anti-influenza drug (oseltamivir ethoxysuccinate) and an influenza vaccine (Ultrix®, SPBNIIVS, Saint Petersburg, Russia) showed effectiveness against the mouse-adapted influenza B virus. Full article
(This article belongs to the Special Issue Non-A Influenza)
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16 pages, 2516 KiB  
Article
Differential Small RNA Responses against Co-Infecting Insect-Specific Viruses in Aedes albopictus Mosquitoes
by Lionel Frangeul, Hervé Blanc, Maria-Carla Saleh and Yasutsugu Suzuki
Viruses 2020, 12(4), 468; https://doi.org/10.3390/v12040468 - 21 Apr 2020
Cited by 11 | Viewed by 3692
Abstract
The mosquito antiviral response has mainly been studied in the context of arthropod-borne virus (arbovirus) infection in female mosquitoes. However, in nature, both female and male mosquitoes are frequently infected with insect-specific viruses (ISVs). ISVs are capable of infecting the reproductive organs of [...] Read more.
The mosquito antiviral response has mainly been studied in the context of arthropod-borne virus (arbovirus) infection in female mosquitoes. However, in nature, both female and male mosquitoes are frequently infected with insect-specific viruses (ISVs). ISVs are capable of infecting the reproductive organs of both sexes and are primarily maintained by vertical transmission. Since the RNA interference (RNAi)-mediated antiviral response plays an important antiviral role in mosquitoes, ISVs constitute a relevant model to study sex-dependent antiviral responses. Using a naturally generated viral stock containing three distinct ISVs, Aedes flavivirus (AEFV), Menghai rhabdovirus (MERV), and Shinobi tetra virus (SHTV), we infected adult Aedes albopictus females and males and generated small RNA libraries from ovaries, testes, and the remainder of the body. Overall, both female and male mosquitoes showed unique small RNA profiles to each co-infecting ISV regardless of the sex or tissue tested. While all three ISVs generated virus-derived siRNAs, only MERV generated virus-derived piRNAs. We also studied the expression of PIWI genes in reproductive tissues and carcasses. In contrast to Piwi5-9, Piwi1-4 were abundantly expressed in ovaries and testes, suggesting that Piwi5-9 are involved in exogenous viral piRNA production. Together, our results show that ISV-infected Aedes albopictus produce viral small RNAs in a virus-specific manner and that male mosquitoes mount a similar small RNA-mediated antiviral response to that of females. Full article
(This article belongs to the Section Insect Viruses)
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15 pages, 1049 KiB  
Article
Phylodynamics Helps to Evaluate the Impact of an HIV Prevention Intervention
by Tetyana I. Vasylyeva, Alexander Zarebski, Pavlo Smyrnov, Leslie D. Williams, Ania Korobchuk, Mariia Liulchuk, Viktoriia Zadorozhna, Georgios Nikolopoulos, Dimitrios Paraskevis, John Schneider, Britt Skaathun, Angelos Hatzakis, Oliver G. Pybus and Samuel R. Friedman
Viruses 2020, 12(4), 469; https://doi.org/10.3390/v12040469 - 20 Apr 2020
Cited by 13 | Viewed by 3129
Abstract
Assessment of the long-term population-level effects of HIV interventions is an ongoing public health challenge. Following the implementation of a Transmission Reduction Intervention Project (TRIP) in Odessa, Ukraine, in 2013–2016, we obtained HIV pol gene sequences and used phylogenetics to identify HIV transmission [...] Read more.
Assessment of the long-term population-level effects of HIV interventions is an ongoing public health challenge. Following the implementation of a Transmission Reduction Intervention Project (TRIP) in Odessa, Ukraine, in 2013–2016, we obtained HIV pol gene sequences and used phylogenetics to identify HIV transmission clusters. We further applied the birth-death skyline model to the sequences from Odessa (n = 275) and Kyiv (n = 92) in order to estimate changes in the epidemic’s effective reproductive number (Re) and rate of becoming uninfectious (δ). We identified 12 transmission clusters in Odessa; phylogenetic clustering was correlated with younger age and higher average viral load at the time of sampling. Estimated Re were similar in Odessa and Kyiv before the initiation of TRIP; Re started to decline in 2013 and is now below Re = 1 in Odessa (Re = 0.4, 95%HPD 0.06–0.75), but not in Kyiv (Re = 2.3, 95%HPD 0.2–5.4). Similarly, estimates of δ increased in Odessa after the initiation of TRIP. Given that both cities shared the same HIV prevention programs in 2013–2019, apart from TRIP, the observed changes in transmission parameters are likely attributable to the TRIP intervention. We propose that molecular epidemiology analysis can be used as a post-intervention effectiveness assessment tool. Full article
(This article belongs to the Special Issue HIV Molecular Epidemiology for Prevention)
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33 pages, 33692 KiB  
Article
Unveiling the Hidden Rules of Spherical Viruses Using Point Arrays
by David P. Wilson
Viruses 2020, 12(4), 467; https://doi.org/10.3390/v12040467 - 20 Apr 2020
Cited by 1 | Viewed by 6271
Abstract
Since its introduction, the Triangulation number has been the most successful and ubiquitous scheme for classifying spherical viruses. However, despite its many successes, it fails to describe the relative angular orientations of proteins, as well as their radial mass distribution within the capsid. [...] Read more.
Since its introduction, the Triangulation number has been the most successful and ubiquitous scheme for classifying spherical viruses. However, despite its many successes, it fails to describe the relative angular orientations of proteins, as well as their radial mass distribution within the capsid. It also fails to provide any critical insight into sites of stability, modifications or possible mutations. We show how classifying spherical viruses using icosahedral point arrays, introduced by Keef and Twarock, unveils new geometric rules and constraints for understanding virus stability and key locations for exterior and interior modifications. We present a modified fitness measure which classifies viruses in an unambiguous and rigorous manner, irrespective of local surface chemistry, steric hinderance, solvent accessibility or Triangulation number. We then use these point arrays to explain the immutable surface loops of bacteriophage MS2, the relative reactivity of surface lysine residues in CPMV and the non-quasi-equivalent flexibility of the HBV dimers. We then explain how point arrays can be used as a predictive tool for site-directed modifications of capsids. This success builds on our previous work showing that viruses place their protruding features along the great circles of the asymmetric unit, demonstrating that viruses indeed adhere to these geometric constraints. Full article
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15 pages, 4456 KiB  
Article
Efficient Mutagenesis of Marek’s Disease Virus-Encoded microRNAs Using a CRISPR/Cas9-Based Gene Editing System
by Jun Luo, Man Teng, Xusheng Zai, Na Tang, Yaoyao Zhang, Ahmedali Mandviwala, Vishwanatha R. A. P. Reddy, Susan Baigent, Yongxiu Yao and Venugopal Nair
Viruses 2020, 12(4), 466; https://doi.org/10.3390/v12040466 - 20 Apr 2020
Cited by 17 | Viewed by 4389
Abstract
The virus-encoded microRNAs (miRNAs) have been demonstrated to have important regulatory roles in herpesvirus biology, including virus replication, latency, pathogenesis and/or tumorigenesis. As an emerging efficient tool for gene editing, the clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 system has been successfully applied [...] Read more.
The virus-encoded microRNAs (miRNAs) have been demonstrated to have important regulatory roles in herpesvirus biology, including virus replication, latency, pathogenesis and/or tumorigenesis. As an emerging efficient tool for gene editing, the clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 system has been successfully applied in manipulating the genomes of large DNA viruses. Herein, utilizing the CRISPR/Cas9 system with a double-guide RNAs transfection/virus infection strategy, we have established a new platform for mutagenesis of viral miRNAs encoded by the Marek’s disease virus serotype 1 (MDV-1), an oncogenic alphaherpesvirus that can induce rapid-onset T-cell lymphomas in chickens. A series of miRNA-knocked out (miR-KO) mutants with deletions of the Meq- or the mid-clustered miRNAs, namely RB-1B∆Meq-miRs, RB-1B∆M9-M2, RB-1B∆M4, RB-1B∆M9 and RB-1B∆M11, were generated from vvMDV strain RB-1B virus. Interestingly, mutagenesis of the targeted miRNAs showed changes in the in vitro virus growth kinetics, which is consistent with that of the in vivo proliferation curves of our previously reported GX0101 mutants produced by the bacterial artificial chromosome (BAC) clone and Rec E/T homologous recombination techniques. Our data demonstrate that the CRISPR/Cas9-based gene editing is a simple, efficient and relatively nondisruptive approach for manipulating the small non-coding genes from the genome of herpesvirus and will undoubtedly contribute significantly to the future progress in herpesvirus biology. Full article
(This article belongs to the Section Animal Viruses)
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15 pages, 2034 KiB  
Review
Nipah Virus: Past Outbreaks and Future Containment
by Vinod Soman Pillai, Gayathri Krishna and Mohanan Valiya Veettil
Viruses 2020, 12(4), 465; https://doi.org/10.3390/v12040465 - 20 Apr 2020
Cited by 67 | Viewed by 19284
Abstract
Viral outbreaks of varying frequencies and severities have caused panic and havoc across the globe throughout history. Influenza, small pox, measles, and yellow fever reverberated for centuries, causing huge burden for economies. The twenty-first century witnessed the most pathogenic and contagious virus outbreaks [...] Read more.
Viral outbreaks of varying frequencies and severities have caused panic and havoc across the globe throughout history. Influenza, small pox, measles, and yellow fever reverberated for centuries, causing huge burden for economies. The twenty-first century witnessed the most pathogenic and contagious virus outbreaks of zoonotic origin including severe acute respiratory syndrome coronavirus (SARS-CoV), Ebola virus, Middle East respiratory syndrome coronavirus (MERS-CoV) and Nipah virus. Nipah is considered one of the world’s deadliest viruses with the heaviest mortality rates in some instances. It is known to cause encephalitis, with cases of acute respiratory distress turning fatal. Various factors contribute to the onset and spread of the virus. All through the infected zone, various strategies to tackle and enhance the surveillance and awareness with greater emphasis on personal hygiene has been formulated. This review discusses the recent outbreaks of Nipah virus in Malaysia, Bangladesh and India, the routes of transmission, prevention and control measures employed along with possible reasons behind the outbreaks, and the precautionary measures to be ensured by private–public undertakings to contain and ensure a lower incidence in the future. Full article
(This article belongs to the Special Issue Emerging Viruses 2020: Surveillance, Prevention, Evolution and Control)
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13 pages, 1132 KiB  
Article
Prevalence and Genomic Diversity of Feline Leukemia Virus in Privately Owned and Shelter Cats in Aburrá Valley, Colombia
by Carolina Ortega, Alida C. Valencia, July Duque-Valencia and Julián Ruiz-Saenz
Viruses 2020, 12(4), 464; https://doi.org/10.3390/v12040464 - 20 Apr 2020
Cited by 8 | Viewed by 3552
Abstract
The feline leukemia virus (FeLV) belongs to the family Retroviridae; it is the first feline retrovirus discovered and one of the agents that has a great impact on cats’ health and the ecology of the feline population worldwide. It is associated with the [...] Read more.
The feline leukemia virus (FeLV) belongs to the family Retroviridae; it is the first feline retrovirus discovered and one of the agents that has a great impact on cats’ health and the ecology of the feline population worldwide. It is associated with the occurrence of several syndromes of fatal diseases, including the development of lymphomas. Studies on FeLV have been reported in Colombia, and most of them have been approached from a clinical point of view. However, only a few studies have focused on the prevalence of the infection, while none have clarified which variant or FeLV viral subgroup is presently circulating in our country. Therefore, the present study investigated the prevalence of the infection associated with the molecular characterization of FeLV present in cats in Aburrá Valley, Colombia. The sampling of privately owned and shelter cats was performed in female (n = 54) and male (n = 46) felines; most of them were seemingly healthy according to the owner’s report, with nonspecific clinical history. Immunoassay confirmed that 59.44% (95% confidence interval (CI) = 49.81–69.06%) of felines were FeLV seropositive. The molecular testing of felines using reverse transcription–polymerase chain reaction and sequencing showed that 30% (30/100) of felines were positive, and the most prevalent subgroup in the Aburrá Valley was FeLV-A. In conclusion, the frequency of leukemia virus, as revealed by molecular and serological tests, is one of the highest reported frequencies to date, and a high molecular variation is shown in the Colombian population. More studies on the behaviour of the virus in feline populations in Columbia are warranted to determine its prevalence throughout the country. Full article
(This article belongs to the Section Animal Viruses)
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19 pages, 3607 KiB  
Article
RNAseq Reveals the Contribution of Interferon Stimulated Genes to the Increased Host Defense and Decreased PPR Viral Replication in Cattle
by Krishnaswamy Gopalan Tirumurugaan, Rahul Mohanchandra Pawar, Gopal Dhinakar Raj, Arthanari Thangavelu, John A. Hammond and Satya Parida
Viruses 2020, 12(4), 463; https://doi.org/10.3390/v12040463 - 20 Apr 2020
Cited by 10 | Viewed by 4942
Abstract
Peste des petits ruminants virus (PPRV) is known to replicate in a wide variety of ruminants causing very species-specific clinical symptoms. Small ruminants (goats and sheep) are susceptible to disease while domesticated cattle and buffalo are dead-end hosts and do not display clinical [...] Read more.
Peste des petits ruminants virus (PPRV) is known to replicate in a wide variety of ruminants causing very species-specific clinical symptoms. Small ruminants (goats and sheep) are susceptible to disease while domesticated cattle and buffalo are dead-end hosts and do not display clinical symptoms. Understanding the host factors that influence differential pathogenesis and disease susceptibility could help the development of better diagnostics and control measures. To study this, we generated transcriptome data from goat and cattle peripheral blood mononuclear cells (PBMC) experimentally infected with PPRV in-vitro. After identifying differentially expressed genes, we further analyzed these immune related pathway genes using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) and selected candidate genes were validated using in-vitro experiments. Upon PPRV infection, we identified 12 and 22 immune related genes that were differentially expressed in goat and cattle respectively. In both species, this included the interferon stimulated genes (ISGs) IFI44, IFI6, IFIT1, IFIT2, IFIT3, ISG15, Mx1, Mx2, OAS1X, RSAD2, IRF7, DDX58 and DHX58 that were transcribed significantly higher in cattle. PPRV replication in goat PBMCs significantly increased the expression of phosphodiesterase 12 (PDE12), a 2′,5′-oligoadenylate degrading enzyme that contributes to the reduced modulation of interferon-regulated gene targets. Finally, a model is proposed for the differential susceptibility between large and small ruminants based on the expression levels of type-I interferons, ISGs and effector molecules. Full article
(This article belongs to the Special Issue Peste des Petits Ruminants (PPR) Eradication: Improved Understanding of Epidemiology, Diagnostics and Vaccine Efficacy)
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12 pages, 1845 KiB  
Article
Synonymous Dinucleotide Usage: A Codon-Aware Metric for Quantifying Dinucleotide Representation in Viruses
by Spyros Lytras and Joseph Hughes
Viruses 2020, 12(4), 462; https://doi.org/10.3390/v12040462 - 20 Apr 2020
Cited by 10 | Viewed by 4266
Abstract
Distinct patterns of dinucleotide representation, such as CpG and UpA suppression, are characteristic of certain viral genomes. Recent research has uncovered vertebrate immune mechanisms that select against specific dinucleotides in targeted viruses. This evidence highlights the importance of systematically examining the dinucleotide composition [...] Read more.
Distinct patterns of dinucleotide representation, such as CpG and UpA suppression, are characteristic of certain viral genomes. Recent research has uncovered vertebrate immune mechanisms that select against specific dinucleotides in targeted viruses. This evidence highlights the importance of systematically examining the dinucleotide composition of viral genomes. We have developed a novel metric, called synonymous dinucleotide usage (SDU), for quantifying dinucleotide representation in coding sequences. Our method compares the abundance of a given dinucleotide to the null hypothesis of equal synonymous codon usage in the sequence. We present a Python3 package, DinuQ, for calculating SDU and other relevant metrics. We have applied this method on two sets of invertebrate- and vertebrate-specific flaviviruses and rhabdoviruses. The SDU shows that the vertebrate viruses exhibit consistently greater under-representation of CpG dinucleotides in all three codon positions in both datasets. In comparison to existing metrics for dinucleotide quantification, the SDU allows for a statistical interpretation of its values by comparing it to a null expectation based on the codon table. Here we apply the method to viruses, but coding sequences of other living organisms can be analysed in the same way. Full article
(This article belongs to the Special Issue Virus Bioinformatics 2020)
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17 pages, 2732 KiB  
Article
Survival of Human Norovirus Surrogates in Water upon Exposure to Thermal and Non-Thermal Antiviral Treatments
by Shu Zhu, Candace Barnes, Sutonuka Bhar, Papa Hoyeck, Annalise N. Galbraith, Divya Devabhaktuni, Stephanie M. Karst, Naim Montazeri and Melissa K. Jones
Viruses 2020, 12(4), 461; https://doi.org/10.3390/v12040461 - 19 Apr 2020
Cited by 12 | Viewed by 3495
Abstract
Human noroviruses are the leading cause of foodborne gastroenteritis worldwide and disease outbreaks have been linked to contaminated surface waters as well as to produce consumption. Noroviruses are extremely stable in water and their presence is being detected with increasing frequency, yet there [...] Read more.
Human noroviruses are the leading cause of foodborne gastroenteritis worldwide and disease outbreaks have been linked to contaminated surface waters as well as to produce consumption. Noroviruses are extremely stable in water and their presence is being detected with increasing frequency, yet there are no viable methods for reducing norovirus contamination in environmental water. Despite this, there is little knowledge regarding the physical and chemical factors that influence the environmental persistence of this pathogen. This study evaluated the impact of common chemical and physical properties of surface water on the stability of murine norovirus and examined the effect of food-safe chitosan microparticles on infectivity of two human norovirus surrogates. While chemical additives had a minor impact on virus survival, chitosan microparticles significantly reduced infectious titers of both murine norovirus and MS2 bacteriophage. Full article
(This article belongs to the Section Animal Viruses)
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25 pages, 1403 KiB  
Review
Battling Neurodegenerative Diseases with Adeno-Associated Virus-Based Approaches
by Olja Mijanović, Ana Branković, Anton V. Borovjagin, Denis V. Butnaru, Evgeny A. Bezrukov, Roman B. Sukhanov, Anastasia Shpichka, Peter Timashev and Ilya Ulasov
Viruses 2020, 12(4), 460; https://doi.org/10.3390/v12040460 - 18 Apr 2020
Cited by 10 | Viewed by 4600
Abstract
Neurodegenerative diseases (NDDs) are most commonly found in adults and remain essentially incurable. Gene therapy using AAV vectors is a rapidly-growing field of experimental medicine that holds promise for the treatment of NDDs. To date, effective delivery of a therapeutic gene into target [...] Read more.
Neurodegenerative diseases (NDDs) are most commonly found in adults and remain essentially incurable. Gene therapy using AAV vectors is a rapidly-growing field of experimental medicine that holds promise for the treatment of NDDs. To date, effective delivery of a therapeutic gene into target cells via AAV has been a major obstacle in the field. Ideally, transgenes should be delivered into the target cells specifically and efficiently, while promiscuous or off-target gene delivery should be minimized to avoid toxicity. In the pursuit of an ideal vehicle for NDD gene therapy, a broad variety of vector systems have been explored. Here we specifically outline the advantages of adeno-associated virus (AAV)-based vector systems for NDD therapy application. In contrast to many reviews on NDDs that can be found in the literature, this review is rather focused on AAV vector selection and their testing in experimental and preclinical NDD models. Preclinical and in vitro data reveal the strong potential of AAV for NDD-related diagnostics and therapeutic strategies. Full article
(This article belongs to the Special Issue Advances in Parvovirus Research 2020)
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17 pages, 3918 KiB  
Article
The Nef Protein of the Macrophage Tropic HIV-1 Strain AD8 Counteracts Human BST-2/Tetherin
by Sebastian Giese, Scott P. Lawrence, Michela Mazzon, Bernadien M. Nijmeijer and Mark Marsh
Viruses 2020, 12(4), 459; https://doi.org/10.3390/v12040459 - 18 Apr 2020
Cited by 5 | Viewed by 2788
Abstract
Bone Marrow Stromal Cell Antigen 2 (BST-2)/tetherin inhibits the release of numerous enveloped viruses by physically tethering nascent particles to infected cells during the process of viral budding from the cell surface. Tetherin also restricts human immunodeficiency virus (HIV), and pandemic main (M) [...] Read more.
Bone Marrow Stromal Cell Antigen 2 (BST-2)/tetherin inhibits the release of numerous enveloped viruses by physically tethering nascent particles to infected cells during the process of viral budding from the cell surface. Tetherin also restricts human immunodeficiency virus (HIV), and pandemic main (M) group HIV type 1s (HIV-1s) are thought to rely exclusively on their Vpu proteins to overcome tetherin-mediated restriction of virus release. However, at least one M group HIV-1 strain, the macrophage-tropic primary AD8 isolate, is unable to express Vpu due to a mutation in its translation initiation codon. Here, using primary monocyte-derived macrophages (MDMs), we show that AD8 Nef protein can compensate for the absence of Vpu and restore virus release to wild type levels. We demonstrate that HIV-1 AD8 Nef reduces endogenous cell surface tetherin levels, physically separating it from the site of viral budding, thus preventing HIV retention. Mechanistically, AD8 Nef enhances internalisation of the long isoform of human tetherin, leading to perinuclear accumulation of the restriction factor. Finally, we show that Nef proteins from other HIV strains also display varying degrees of tetherin antagonism. Overall, we show that M group HIV-1s can use an accessory protein other than Vpu to antagonise human tetherin. Full article
(This article belongs to the Special Issue Role of Myeloid Cells in Viral Infections)
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14 pages, 2209 KiB  
Article
Human West Nile Virus Lineage 2 Infection: Epidemiological, Clinical, and Virological Findings
by Monia Pacenti, Alessandro Sinigaglia, Elisa Franchin, Silvana Pagni, Enrico Lavezzo, Fabrizio Montarsi, Gioia Capelli and Luisa Barzon
Viruses 2020, 12(4), 458; https://doi.org/10.3390/v12040458 - 18 Apr 2020
Cited by 20 | Viewed by 3382
Abstract
West Nile virus (WNV) lineage 2 is expanding and causing large outbreaks in Europe. In this study, we analyzed the epidemiological, clinical, and virological features of WNV lineage 2 infection during the large outbreak that occurred in northern Italy in 2018. The study [...] Read more.
West Nile virus (WNV) lineage 2 is expanding and causing large outbreaks in Europe. In this study, we analyzed the epidemiological, clinical, and virological features of WNV lineage 2 infection during the large outbreak that occurred in northern Italy in 2018. The study population included 86 patients with neuroinvasive disease (WNND), 307 with fever (WNF), and 34 blood donors. Phylogenetic analysis of WNV full genome sequences from patients’ samples showed that the virus belonged to the widespread central/southern European clade of WNV lineage 2 and was circulating in the area at least since 2014. The incidence of WNND and WNF progressively increased with age and was higher in males than in females. Among WNND patients, the case fatality rate was 22%. About 70% of blood donors reported symptoms during follow-up. Within the first week after symptom onset, WNV RNA was detectable in the blood or urine of 80% of patients, while 20% and 40% of WNND and WNF patients, respectively, were WNV IgM-seronegative. In CSF samples of WNND patients, WNV RNA was typically detectable when WNV IgM antibodies were absent. Blunted or no WNV IgM response and high WNV IgG levels were observed in seven patients with previous flavivirus immunity. Full article
(This article belongs to the Special Issue Emerging Arboviruses)
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14 pages, 2171 KiB  
Article
Orthohantavirus Isolated in Reservoir Host Cells Displays Minimal Genetic Changes and Retains Wild-Type Infection Properties
by Tomas Strandin, Teemu Smura, Paula Ahola, Kirsi Aaltonen, Tarja Sironen, Jussi Hepojoki, Isabella Eckerle, Rainer G. Ulrich, Olli Vapalahti, Anja Kipar and Kristian M. Forbes
Viruses 2020, 12(4), 457; https://doi.org/10.3390/v12040457 - 17 Apr 2020
Cited by 10 | Viewed by 2816
Abstract
Orthohantaviruses are globally emerging zoonotic pathogens. While the reservoir host role of several rodent species is well-established, detailed research on the mechanisms of host-othohantavirus interactions has been constrained by the lack of an experimental system that is able to effectively replicate natural infections [...] Read more.
Orthohantaviruses are globally emerging zoonotic pathogens. While the reservoir host role of several rodent species is well-established, detailed research on the mechanisms of host-othohantavirus interactions has been constrained by the lack of an experimental system that is able to effectively replicate natural infections in controlled settings. Here we report the isolation, and genetic and phenotypic characterization of a novel Puumala orthohantavirus (PUUV) in cells derived from its reservoir host, the bank vole. The isolation process resulted in cell culture infection that evaded antiviral responses, persisted cell passaging, and had minor viral genome alterations. Critically, experimental infections of bank voles with the new isolate resembled natural infections in terms of viral load and host cell distribution. When compared to an attenuated Vero E6 cell-adapted PUUV Kazan strain, the novel isolate demonstrated delayed virus-specific humoral responses. A lack of virus-specific antibodies was also observed during experimental infections with wild-type PUUV, suggesting that delayed seroconversion could be a general phenomenon during orthohantavirus infection in reservoir hosts. Our results demonstrate that orthohantavirus isolation on cells derived from a vole reservoir host retains wild-type infection properties and should be considered the method of choice for experimental infection models to replicate natural processes. Full article
(This article belongs to the Special Issue Virus Ecology and Evolution: Current Research and Future Directions)
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20 pages, 4464 KiB  
Article
ORF Ι of Mycovirus SsNSRV-1 is Associated with Debilitating Symptoms of Sclerotinia sclerotiorum
by Zhixiao Gao, Junyan Wu, Daohong Jiang, Jiatao Xie, Jiasen Cheng and Yang Lin
Viruses 2020, 12(4), 456; https://doi.org/10.3390/v12040456 - 17 Apr 2020
Cited by 9 | Viewed by 3861
Abstract
We previously identified Sclerotinia sclerotiorum negative-stranded virus 1 (SsNSRV-1), the first (−) ssRNA mycovirus, associated with hypovirulence of its fungal host Sclerotinia sclerotiorum. In this study, functional analysis of Open Reading Frame Ι (ORF Ι) of SsNSRV-1 was performed. The [...] Read more.
We previously identified Sclerotinia sclerotiorum negative-stranded virus 1 (SsNSRV-1), the first (−) ssRNA mycovirus, associated with hypovirulence of its fungal host Sclerotinia sclerotiorum. In this study, functional analysis of Open Reading Frame Ι (ORF Ι) of SsNSRV-1 was performed. The integration and expression of ORF Ι led to defects in hyphal tips, vegetative growth, and virulence of the mutant strains of S. sclerotiorum. Further, differentially expressed genes (DEGs) responding to the expression of ORF Ι were identified by transcriptome analysis. In all, 686 DEGs consisted of 267 up-regulated genes and 419 down-regulated genes. DEGs reprogramed by ORF Ι were relevant to secretory proteins, pathogenicity, transcription, transmembrane transport, protein biosynthesis, modification, and metabolism. Alternative splicing was also detected in all mutant strains, but not in hypovirulent strain AH98, which was co-infected by SsNSRV-1 and Sclerotinia sclerotiorum hypovirus 1 (SsHV-1). Thus, the integrity of SsNSRV-1 genome may be necessary to protect viral mRNA from splicing and inactivation by the host. Taken together, the results suggested that protein ORF Ι could regulate the transcription, translation, and modification of host genes in order to facilitate viral proliferation and reduce the virulence of the host. Therefore, ORF Ι may be a potential gene used for the prevention of S. sclerotiorum. Full article
(This article belongs to the Collection Mycoviruses)
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12 pages, 1335 KiB  
Article
Reverse Genetics System for Shuni Virus, an Emerging Orthobunyavirus with Zoonotic Potential
by Judith Oymans, Paul J. Wichgers Schreur, Sophie van Oort, Rianka Vloet, Marietjie Venter, Gorben P. Pijlman, Monique M. van Oers and Jeroen Kortekaas
Viruses 2020, 12(4), 455; https://doi.org/10.3390/v12040455 - 17 Apr 2020
Cited by 9 | Viewed by 3351
Abstract
The genus Orthobunyavirus (family Peribunyaviridae, order Bunyavirales) comprises over 170 named mosquito- and midge-borne viruses, several of which cause severe disease in animals or humans. Their three-segmented genomes enable reassortment with related viruses, which may result in novel viruses with altered [...] Read more.
The genus Orthobunyavirus (family Peribunyaviridae, order Bunyavirales) comprises over 170 named mosquito- and midge-borne viruses, several of which cause severe disease in animals or humans. Their three-segmented genomes enable reassortment with related viruses, which may result in novel viruses with altered host or tissue tropism and virulence. One such reassortant, Schmallenberg virus (SBV), emerged in north-western Europe in 2011. Shuni virus (SHUV) is an orthobunyavirus related to SBV that is associated with neurological disease in horses in southern Africa and recently caused an outbreak manifesting with neurological disease and birth defects among ruminants in Israel. The zoonotic potential of SHUV was recently underscored by its association with neurological disease in humans. We here report a reverse genetics system for SHUV and provide first evidence that the non-structural (NSs) protein of SHUV functions as an antagonist of host innate immune responses. We furthermore report the rescue of a reassortant containing the L and S segments of SBV and the M segment of SHUV. This novel reverse genetics system can now be used to study SHUV virulence and tropism, and to elucidate the molecular mechanisms that drive reassortment events. Full article
(This article belongs to the Section Animal Viruses)
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9 pages, 714 KiB  
Communication
Retrieval of the Complete Coding Sequence of the UK-Endemic Tatenale Orthohantavirus Reveals Extensive Strain Variation and Supports Its Classification as a Novel Species
by Joseph G. Chappell, Theocharis Tsoleridis, Okechukwu Onianwa, Gabby Drake, Ian Ashpole, Phillipa Dobbs, William Edema, Frederick Kumi-Ansah, Malcolm Bennett, Rachael E. Tarlinton, Jonathan K. Ball and C. Patrick McClure
Viruses 2020, 12(4), 454; https://doi.org/10.3390/v12040454 - 17 Apr 2020
Cited by 4 | Viewed by 4456
Abstract
Orthohantaviruses are globally distributed viruses, associated with rodents and other small mammals. However, data on the circulation of orthohantaviruses within the UK, particularly the UK-endemic Tatenale virus, is sparse. In this study, 531 animals from five rodent species were collected from two locations [...] Read more.
Orthohantaviruses are globally distributed viruses, associated with rodents and other small mammals. However, data on the circulation of orthohantaviruses within the UK, particularly the UK-endemic Tatenale virus, is sparse. In this study, 531 animals from five rodent species were collected from two locations in northern and central England and screened using a degenerate, pan- orthohantavirus RT-PCR assay. Tatenale virus was detected in a single field vole (Microtus agrestis) from central England and twelve field voles from northern England. Unbiased high-throughput sequencing of the central English strain resulted in the recovery of the complete coding sequence of a novel strain of Tatenale virus, whilst PCR-primer walking of the northern English strain recovered almost complete coding sequence of a previously identified strain. These findings represented the detection of a third lineage of Tatenale virus in the United Kingdom and extended the known geographic distribution of these viruses from northern to central England. Furthermore, the recovery of the complete coding sequence revealed that Tatenale virus was sufficiently related to the recently identified Traemersee virus, to meet the accepted criteria for classification as a single species of orthohantavirus. Full article
(This article belongs to the Section Animal Viruses)
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