Home | Journal of Virology

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Metabolic Syndrome and Viral Pathogenesis: Lessons from Influenza and Coronaviruses Metabolic syndrome increases the risk of severe disease due to viral infection. Yet few studies have assessed the pathogenesis of respiratory viruses in high-risk populations. Here, we summarize how metabolic dysregulation impairs immune responses, and we define the role of metabolism during influenza virus and coronavirus infections. We also discuss the use of various in vitro, in vivo, and ex vivo models to... Maria Smith, Rebekah Honce, Stacey Schultz-Cherry A Virion-Based Assay for Glycoprotein Thermostability Reveals Key Determinants of Filovirus Entry and Its Inhibition The development of Ebola virus countermeasures is challenged by our limited understanding of cell entry, especially at the step of membrane fusion. The surface-exposed viral protein, GP, mediates membrane fusion and undergoes major structural rearrangements during this process. The stability of GP at elevated temperatures (thermostability) can provide insights into its capacity to undergo these rearrangements. Here, we describe a new... Robert H. Bortz, Anthony C. Wong, Michael G. Grodus, Hannah S. Recht, Marc C. Pulanco, Gorka Lasso, Simon J. Anthony, Eva Mittler, Rohit K. Jangra, Kartik Chandran Reconstitution of an RNA Virus Replicase in Artificial Giant Unilamellar Vesicles Supports Full Replication and Provides Protection for the Double-Stranded RNA Replication Intermediate Understanding the mechanism of replication of positive-strand RNA viruses, which are major pathogens of plants, animals, and humans, can lead to new targets for antiviral interventions. These viruses subvert intracellular membranes for virus replication and coopt numerous host proteins, whose functions during virus replication are not yet completely defined. To dissect the roles of various host factors in Tomato bushy stunt virus... Nikolay Kovalev, Judit Pogany, Peter D. Nagy Zika Virus Subgenomic Flavivirus RNA Generation Requires Cooperativity between Duplicated RNA Structures That Are Essential for Productive Infection in Human Cells Flaviviruses are important emerging and reemerging human pathogens. Understanding the molecular mechanisms for viral replication and evasion of host antiviral responses is relevant to development of control strategies. Flavivirus infections produce viral noncoding RNAs, known as sfRNAs, involved in viral replication and pathogenesis. In this study, we dissected molecular determinants for Zika virus sfRNA generation in the two natural... Horacio M. Pallarés, Guadalupe Soledad Costa Navarro, Sergio M. Villordo, Fernando Merwaiss, Luana de Borba, Maria M. Gonzalez Lopez Ledesma, Diego S. Ojeda, Annabelle Henrion-Lacritick, Maria A. Morales, Cintia Fabri, María Carla Saleh, Andrea V. Gamarnik Reactivation of Epstein-Barr Virus by HIF-1α Requires p53 EBV, a human herpesvirus, is latently present in most nasopharyngeal carcinomas, Burkitt lymphomas, and some gastric cancers. To develop a lytic-induction therapy for treating patients with EBV-associated cancers, we need a way to efficiently reactivate EBV into lytic replication. EBV’s BZLF1 gene product, Zta, usually controls this reactivation switch. We previously showed that HIF-1α binds the BZLF1 gene promoter,... Richard J. Kraus, Blue-leaf A. Cordes, Saraniya Sathiamoorthi, Parita Patel, Xueying Yuan, Tawin Iempridee, Xianming Yu, Denis L. Lee, Paul F. Lambert, Janet E. Mertz Expression of Separate Heterologous Proteins from the Rotavirus NSP3 Genome Segment Using a Translational 2A Stop-Restart Element Rotaviruses are a major cause of severe gastroenteritis in infants and young children. Recently, a highly efficient reverse genetics system was developed that allows genetic manipulation of the rotavirus segmented double-stranded RNA genome. Using the reverse genetics system, we show that it is possible to modify one of the rotavirus genome segments (segment 7) such that virus gains the capacity to express a separate heterologous... Asha A. Philip, John T. Patton Sp3 Transcription Factor Cooperates with the Kaposi’s Sarcoma-Associated Herpesvirus ORF50 Protein To Synergistically Activate Specific Viral and Cellular Gene Promoters Despite the critical role of ORF50 in the KSHV latent-to-lytic switch, the molecular mechanism by which ORF50 activates its downstream target genes, especially those that encode the viral DNA replication enzymes, is not yet fully understood. Here, we find that ORF50 can cooperate with Sp3 to synergistically activate promoters of the viral ORF56 (primase), ORF21 (thymidine kinase), and ORF60 (ribonucleotide reductase) genes via similar... Li-Yu Chen, Lee-Wen Chen, Kuo-Ti Peng, Chien-Hui Hung, Pey-Jium Chang, Shie-Shan Wang An Optimized Reverse Genetics System Suitable for Efficient Recovery of Simian, Human, and Murine-Like Rotaviruses Group A rotavirus (RV) remains as the single most important cause of severe acute gastroenteritis among infants and young children worldwide. An entirely plasmid-based reverse genetics (RG) system was recently developed, opening new ways for in-depth molecular study of RV. Despite several improvements to further optimize the RG efficiency, it has been reported that current strategies do not enable the rescue of all cultivatable RV... Liliana Sánchez-Tacuba, Ningguo Feng, Nathan J. Meade, Kenneth H. Mellits, Philippe H. Jaïs, Linda L. Yasukawa, Theresa K. Resch, Baoming Jiang, Susana López, Siyuan Ding, Harry B. Greenberg Metatranscriptomic Analysis of Virus Diversity in Urban Wild Birds with Paretic Disease Wildlife naturally harbor a diverse array of infectious microorganisms and can be a source of novel diseases in domestic animals and human populations. Using unbiased RNA sequencing, we identified highly diverse viruses in native birds from Australian urban environments presenting with paresis. This research included the clinical investigation and description of poorly understood recurring syndromes of unknown etiology: clenched claw... Wei-Shan Chang, John-Sebastian Eden, Jane Hall, Mang Shi, Karrie Rose, Edward C. Holmes Characterization of a Novel Alphaherpesvirus Isolated from the Fruit Bat Pteropus lylei in Vietnam A novel bat alphaherpesvirus, Pteropus lylei-associated alphaherpesvirus (PLAHV), was isolated from urine of the fruit bat Pteropus lylei in Vietnam. The whole-genome sequence was determined and was predicted to include 72 open reading frames in the 144,008-bp genome. PLAHV is circulating in a species of fruit bats, Pteropus lylei, in Asia. This study expands the knowledge on bat-associated alphaherpesvirology... Takuya Inagaki, Souichi Yamada, Hikaru Fujii, Tomoki Yoshikawa, Miho Shibamura, Shizuko Harada, Shuetsu Fukushi, Mai Quynh Le, Co Thach Nguyen, Thi Thu Thuy Nguyen, Thanh Thuy Nguyen, Thanh Thuy Nguyen, Van Tay Quach, Vu Dinh Thong, Kazuki Mori, Michihito Sasaki, Agus Setiyono, Ekowati Handharyani, Haruko Takeyama, Futoshi Hasebe, Masayuki Saijo Inactivation of Genes by Frameshift Mutations Provides Rapid Adaptation of an Attenuated Vaccinia Virus Gene inactivation is considered to be an important driver of orthopoxvirus evolution. Whereas cowpox virus contains intact orthologs of genes present in each orthopoxvirus species, numerous genes are inactivated in all other members of the genus. Inactivation of additional genes can occur upon extensive passaging of orthopoxviruses in cell culture leading to attenuation in vivo, a strategy for making vaccines. Whether... Tatiana G. Senkevich, Erik K. Zhivkoplias, Andrea S. Weisberg, Bernard Moss Phosphoregulation of a Conserved Herpesvirus Tegument Protein by a Virally Encoded Protein Kinase in Viral Pathogenicity and Potential Linkage between Its Evolution and Viral Phylogeny It has been hypothesized that the evolution of protein phosphoregulation drives phenotypic diversity across species of organisms, which impacts fitness during their evolution. However, there is a lack of information regarding linkage between the evolution of viral phosphoregulation and the phylogeny of virus species. In this study, we clarified the novel HSV-2 Us3 phosphoregulation of UL7 in infected cells, which is important for viral... Misato Shibazaki, Akihisa Kato, Kosuke Takeshima, Jumpei Ito, Mai Suganami, Naoto Koyanagi, Yuhei Maruzuru, Kei Sato, Yasushi Kawaguchi Genomic Analysis of Early SARS-CoV-2 Variants Introduced in Mexico Understanding the introduction, spread, and establishment of SARS-CoV-2 within distinct human populations as well as the evolution of the pandemics is crucial to implement effective control strategies. In this work, we report that the initial virus strains introduced in Mexico came from Europe and the United States and that the virus was circulating locally in the country as early as mid-March. We also found evidence for early local... Blanca Taboada, Joel Armando Vazquez-Perez, José Esteban Muñoz-Medina, Pilar Ramos-Cervantes, Marina Escalera-Zamudio, Celia Boukadida, Alejandro Sanchez-Flores, Pavel Isa, Edgar Mendieta-Condado, José A. Martínez-Orozco, Eduardo Becerril-Vargas, Jorge Salas-Hernández, Ricardo Grande, Carolina González-Torres, Francisco Javier Gaytán-Cervantes, Gloria Vazquez, Francisco Pulido, Adnan Araiza-Rodríguez, Fabiola Garcés-Ayala, Cesar Raúl González-Bonilla, Concepción Grajales-Muñiz, Víctor Hugo Borja-Aburto, Gisela Barrera-Badillo, Susana López, Lucía Hernández-Rivas, Rogelio Perez-Padilla, Irma López-Martínez, Santiago Ávila-Ríos, Guillermo Ruiz-Palacios, José Ernesto Ramírez-González, Carlos F. Arias LY6E Restricts Entry of Human Coronaviruses, Including Currently Pandemic SARS-CoV-2 Virus entry into host cells is one of the key determinants of host range and cell tropism and is subjected to the control of host innate and adaptive immune responses. In the last decade, several interferon-inducible cellular proteins, including IFITMs, GILT, ADAP2, 25CH, and LY6E, had been identified to modulate the infectious entry of a variety of viruses. Particularly, LY6E was recently identified as a host factor that facilitates... Xuesen Zhao, Shuangli Zheng, Danying Chen, Mei Zheng, Xinglin Li, Guoli Li, Hanxin Lin, Jinhong Chang, Hui Zeng, Ju-Tao Guo Broad and Differential Animal Angiotensin-Converting Enzyme 2 Receptor Usage by SARS-CoV-2 SARS-CoV-2 uses human ACE2 as a primary receptor for host cell entry. Viral entry mediated by the interaction of ACE2 with spike protein largely determines host range and is the major constraint to interspecies transmission. We examined the receptor activity of 14 ACE2 orthologs and found that wild-type and mutant SARS-CoV-2 lacking the furin cleavage site in S protein could utilize ACE2 from a broad range of animal species to enter... Xuesen Zhao, Danying Chen, Robert Szabla, Mei Zheng, Guoli Li, Pengcheng Du, Shuangli Zheng, Xinglin Li, Chuan Song, Rui Li, Ju-Tao Guo, Murray Junop, Hui Zeng, Hanxin Lin H9N2 Influenza Virus Infections in Human Cells Require a Balance between Neuraminidase Sialidase Activity and Hemagglutinin Receptor Affinity H9N2 avian influenza (AI) virus, one of the most prevalent AI viruses, has caused repeated poultry and human infections, posing a huge public health risk. The H9N2 virus has diversified into multiple lineages, with the G1 lineage being the most prevalent worldwide. In this study, we isolated G1 variants carrying an 8-amino-acid deletion in their NA stalk, which is, to our knowledge, the longest deletion found in H9N2 viruses in the... Yasuha Arai, Emad Mohamed Elgendy, Tomo Daidoji, Madiha Salah Ibrahim, Takao Ono, Nongluk Sriwilaijaroen, Yasuo Suzuki, Takaaki Nakaya, Kazuhiko Matsumoto, Yohei Watanabe Murine Leukemia Virus P50 Protein Counteracts APOBEC3 by Blocking Its Packaging MLV has existed in mice for at least a million years, in spite of the existence of host restriction factors that block infection. Although MLV is considered a simple retrovirus compared to lentiviruses, it does encode proteins generated from alternatively spliced RNAs. Here, we show that P50, generated from an alternatively spliced RNA encoded in gag, counteracts APOBEC3 by blocking its packaging. MLV also encodes a protein,... Wenming Zhao, Charbel Akkawi, Marylène Mougel, Susan R. Ross PD-L1 Checkpoint Inhibition Narrows the Antigen-Specific T Cell Receptor Repertoire in Chronic Lymphocytic Choriomeningitis Virus Infection Checkpoint inhibitors are effective immunotherapeutics to restore cancer- and virus-induced exhausted CD8+ T cells, by enhancing the quality and survival of immune responses. Although checkpoint inhibitors are already used as therapy against various cancers, not much is known about their multifaceted impact on the exhausted CD8+ T cell receptor (TCR) repertoire. This report describes for the first time the... S. Klein, D. Ghersi, M. P. Manns, I. Prinz, M. Cornberg, A. R. M. Kraft Swine Promyelocytic Leukemia Isoform II Inhibits Pseudorabies Virus Infection by Suppressing Viral Gene Transcription in Promyelocytic Leukemia Nuclear Bodies PML-NBs are nuclear sites that mediate the antiviral restriction of alphaherpesvirus gene expression and replication. However, the contribution of each PML isoform to this activity of PML-NBs is not well characterized. Using PRV and its natural host swine cells as a system, we have discovered that the unique C terminus of sPML isoform II is required for PML-NBs to inhibit PRV infection by directly engaging in repression of viral gene... Cuilian Yu, Aotian Xu, Yue Lang, Chao Qin, Mengdong Wang, Xiufang Yuan, Shengfu Sun, Wenhai Feng, Chao Gao, Jinwen Chen, Rui Zhang, Jun Tang Inhibition of Human Adenovirus Replication by the Importin α/β1 Nuclear Import Inhibitor Ivermectin Human adenoviruses (HAdVs) represent a ubiquitous and clinically important pathogen without an effective antiviral treatment. HAdV infections typically cause mild symptoms; however, individuals such as children, those with underlying conditions, and those with compromised immune systems can develop severe disseminated disease. Our results demonstrate that ivermectin, an FDA-approved antiparasitic agent, is effective at inhibiting... Cason R. King, Tanner M. Tessier, Mackenzie J. Dodge, Jason B. Weinberg, Joe S. Mymryk Dimerization of Dengue Virus E Subunits Impacts Antibody Function and Domain Focus Dengue virus vaccine development is particularly challenging because vaccines have to provide protection against four different dengue virus stereotypes. The leading dengue virus vaccine candidates in clinical testing are all based on live-virus vaccine platforms and struggle to induce balanced immunity. Envelope subunit antigens have the potential to overcome these limitations but have historically performed poorly as vaccine antigens... Ashlie Thomas, Devina J. Thiono, Stephan T. Kudlacek, John Forsberg, Lakshmanane Premkumar, Shaomin Tian, Brian Kuhlman, Aravinda M. de Silva, Stefan W. Metz Cell Fusion Induced by a Fusion-Active Form of Human Cytomegalovirus Glycoprotein B (gB) Is Inhibited by Antibodies Directed at Antigenic Domain 5 in the Ectodomain of gB HCMV is a major global health concern, and antiviral chemotherapy remains problematic due to toxicity of available compounds and the emergence of drug-resistant viruses. Thus, an HCMV vaccine represents a priority for both governmental and pharmaceutical research programs. A major obstacle for the development of a vaccine is a lack of knowledge of the nature and specificities of protective immune responses that should be induced by such... Nina Reuter, Barbara Kropff, Julia Karin Schneiderbanger, Mira Alt, Adalbert Krawczyk, Christian Sinzger, Thomas H. Winkler, William J. Britt, Michael Mach, Marco Thomas Limited Cross-Protection Provided by Prior Infection Contributes to High Prevalence of Influenza D Viruses in Cattle Influenza D viruses (IDVs) are panzootic in multiple animal hosts, but the underlying mechanism is unclear. Through multiple years of surveillance in the same order-buyer cattle facility, 32 IDV isolates were recovered from both healthy and sick animals, including those with evident antibodies against IDV. Active reassortment occurred in the cattle within this facility and in those across other areas, and multiple reassortants... Xiu-Feng Wan, Lucas Ferguson, Justine Oliva, Adam Rubrum, Laura Eckard, Xiaojian Zhang, Amelia R. Woolums, Adrien Lion, Gilles Meyer, Shin Murakami, Wenjun Ma, Taisuke Horimoto, Richard Webby, Mariette F. Ducatez, William Epperson Interferon-Induced Protein 44 and Interferon-Induced Protein 44-Like Restrict Replication of Respiratory Syncytial Virus RSV infects all children under 2 years of age, but only a subset of children get severe disease. We hypothesize that susceptibility to severe RSV necessitating hospitalization in children without predefined risk factors is, in part, mediated at the antiviral gene level. However, there is a large array of antiviral genes, particularly in the ISG family, the mechanism of which is poorly understood. Having previously identified IFI44 and... D. C. Busse, D. Habgood-Coote, S. Clare, C. Brandt, I. Bassano, M. Kaforou, J. Herberg, M. Levin, J.-F. Eléouët, P. Kellam, J. S. Tregoning Serpentoviruses: More than Respiratory Pathogens During the last years, python nidoviruses (now reclassified as serpentoviruses) have become a primary cause of fatal disease in pythons. Serpentoviruses represent a threat to captive snake collections, as they spread rapidly and can be associated with high morbidity and mortality. Our study indicates that, different from previous evidence, the viruses do not only affect the respiratory tract, but can spread in the entire body with blood... Eva Dervas, Jussi Hepojoki, Teemu Smura, Barbara Prähauser, Katharina Windbichler, Sandra Blümich, Antonio Ramis, Udo Hetzel, Anja Kipar The SARS-CoV-2 N Protein Is a Good Component in a Vaccine Gustaf Ahlén, Lars Frelin, Negin Nikouyan, Friedemann Weber, Urban Höglund, Olivia Larsson, Marie Westman, Ola Tuvesson, Eva-karin Gidlund, Matteo Cadossi, Sofia Appelberg, Ali Mirazimi, Matti Sällberg and for the OPENCORONA ConsortiumJournal of Virology (JVI) explores the nature of viruses, reporting important new discoveries and pointing to new directions in research.For Authors

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