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Table of Contents

February 2019; Volume 93,Issue 4

Spotlight

  • Free
    Articles of Significant Interest in This Issue
    Spotlight
    Articles of Significant Interest in This Issue

Meeting Review

  • The 13th International Double-Stranded RNA Virus Symposium, Houffalize, Belgium, 24 to 28 September 2018
    Meeting Review
    The 13th International Double-Stranded RNA Virus Symposium, Houffalize, Belgium, 24 to 28 September 2018

    The triennial International Double-Stranded RNA Virus Symposium, this year organized by J. Matthijnssens, J.

    Ulrich Desselberger

Structure and Assembly

  • The Ectodomain of the Vaccinia Virus Glycoprotein A34 Is Required for Cell Binding by Extracellular Virions and Contains a Large Region Capable of Interaction with Glycoprotein B5
    Structure and Assembly
    The Ectodomain of the Vaccinia Virus Glycoprotein A34 Is Required for Cell Binding by Extracellular Virions and Contains a Large Region Capable of Interaction with Glycoprotein B5

    Previous studies have shown that the vaccinia virus glycoproteins A34 and B5 interact, and in the absence of A34, B5 is mislocalized and not incorporated into extracellular virions. Here, using a transient-transfection assay, residues 80 to 130 of the ectodomain of A34 were determined to be sufficient for interaction with B5. Recombinant viruses expressing A34 with a full, partial, or no B5 interaction site were constructed and...

    Stephanie R. Monticelli, Amalia K. Earley, Jessica Tate, Brian M. Ward
  • Packaging of the Influenza Virus Genome Is Governed by a Plastic Network of RNA- and Nucleoprotein-Mediated Interactions
    Structure and Assembly
    Packaging of the Influenza Virus Genome Is Governed by a Plastic Network of RNA- and Nucleoprotein-Mediated Interactions

    The genome of influenza A virus is organized into eight viral ribonucleoproteins (vRNPs); this provides evolutionary advantages but complicates genome packaging. Although it has been shown that RNA packaging sequences and specific amino acids in the viral nucleoprotein (NP), both components of each vRNP, ensure selective packaging of one copy of each vRNP per virus particle, the required RNA-RNA and RNA-NP interactions remain largely...

    Hardin Bolte, Miruna E. Rosu, Elena Hagelauer, Adolfo García-Sastre, Martin Schwemmle
  • The Alphavirus E2 Membrane-Proximal Domain Impacts Capsid Interaction and Glycoprotein Lattice Formation
    Structure and Assembly
    The Alphavirus E2 Membrane-Proximal Domain Impacts Capsid Interaction and Glycoprotein Lattice Formation

    Alphaviruses include important human pathogens such as Chikungunya and the encephalitic alphaviruses. There are currently no licensed alphavirus vaccines or effective antiviral therapies, and more molecular information on virus particle structure and function is needed. Here, we highlight the important role of the E2 juxtamembrane D-loop in mediating virus budding and particle production. Our results demonstrated that this E2 region...

    Emily A. Byrd, Margaret Kielian

Genome Replication and Regulation of Viral Gene Expression

  • Directed Nucleosome Sliding during the Formation of the Simian Virus 40 Particle Exposes DNA Sequences Required for Early Transcription
    Genome Replication and Regulation of Viral Gene Expression
    Directed Nucleosome Sliding during the Formation of the Simian Virus 40 Particle Exposes DNA Sequences Required for Early Transcription

    For a virus to complete infection, it must produce a new virus particle in which the genome is able to support a new infection. This is particularly important for viruses like simian virus 40 (SV40), which exist as chromatin throughout their life cycles, since chromatin structure plays a major role in the regulation of the life cycle. In order to determine the role of SV40 chromatin structure late in infection, we mapped the locations...

    Meera Ajeet Kumar, Karine Kasti, Lata Balakrishnan, Barry Milavetz
  • The <em>Herpesviridae</em> Conserved Multifunctional Infected-Cell Protein 27 (ICP27) Is Important but Not Required for Replication and Oncogenicity of Marek’s Disease Alphaherpesvirus
    Genome Replication and Regulation of Viral Gene Expression
    The Herpesviridae Conserved Multifunctional Infected-Cell Protein 27 (ICP27) Is Important but Not Required for Replication and Oncogenicity of Marek’s Disease Alphaherpesvirus

    Marek’s disease (MD) is a devastating oncogenic disease that affects the poultry industry and is caused by MD alphaherpesvirus (MDV). Current vaccines block induction of disease but do not block chicken-to-chicken transmission. There is a knowledge gap in our understanding of how MDV spreads from chicken to chicken. We studied the Herpesviridae conserved ICP27 regulatory protein in cell culture and during MDV infection in...

    Nagendraprabhu Ponnuraj, Yung-Tien Tien, Widaliz Vega-Rodriguez, Andrea Krieter, Keith W. Jarosinski

Genetic Diversity and Evolution

  • Existing Host Range Mutations Constrain Further Emergence of RNA Viruses
    Genetic Diversity and Evolution
    Existing Host Range Mutations Constrain Further Emergence of RNA Viruses

    RNA viruses mutate rapidly and frequently expand their host ranges to infect novel hosts, leading to serial host shifts. Using an RNA bacteriophage model system (Pseudomonas phage φ6), we studied the impact of preexisting host range mutations on another host range expansion. Results from both clonal Sanger and Illumina sequencing show that extant host range mutations dramatically narrow the neighborhood of potential host range...

    Lele Zhao, Mansha Seth-Pasricha, Dragoş Stemate, Alvin Crespo-Bellido, Jacqueline Gagnon, Jeremy Draghi, Siobain Duffy
  • Epidemiological Evidence for Lineage-Specific Differences in the Risk of Inapparent Chikungunya Virus Infection
    Genetic Diversity and Evolution
    Epidemiological Evidence for Lineage-Specific Differences in the Risk of Inapparent Chikungunya Virus Infection

    Chikungunya virus (CHIKV) is an understudied threat to human health. During the 2015 chikungunya epidemic in Managua, Nicaragua, we estimated the ratio of symptomatic to asymptomatic CHIKV infections, which is important for understanding transmission dynamics and the public health impact of CHIKV. This index cluster study identified and monitored persons at risk of infection, enabling capture of asymptomatic infections. We estimated...

    Fausto Bustos Carrillo, Damaris Collado, Nery Sanchez, Sergio Ojeda, Brenda Lopez Mercado, Raquel Burger-Calderon, Lionel Gresh, Aubree Gordon, Angel Balmaseda, Guillermina Kuan, Eva Harris
  • Open Access
    A Novel Type of Influenza A Virus-Derived Defective Interfering Particle with Nucleotide Substitutions in Its Genome
    Genetic Diversity and Evolution
    A Novel Type of Influenza A Virus-Derived Defective Interfering Particle with Nucleotide Substitutions in Its Genome

    Defective interfering particles (DIPs) typically contain a highly deleted form of the viral genome, rendering them defective in virus replication. Yet upon complementation through coinfection with fully infectious standard virus (STV), interference with the viral life cycle can be observed, leading to suppressed STV replication and the release of mainly noninfectious DIPs. Interestingly, recent research indicates that DIPs may serve as...

    Sascha Young Kupke, Dietmar Riedel, Timo Frensing, Pawel Zmora, Udo Reichl
  • Capture of a Hyena-Specific Retroviral Envelope Gene with Placental Expression Associated in Evolution with the Unique Emergence among Carnivorans of Hemochorial Placentation in Hyaenidae
    Genetic Diversity and Evolution
    Capture of a Hyena-Specific Retroviral Envelope Gene with Placental Expression Associated in Evolution with the Unique Emergence among Carnivorans of Hemochorial Placentation in Hyaenidae

    The placenta is the most diverse organ among mammals, due in part to stochastic capture of retroviral envelope genes. In carnivorans, capture of syncytin-Car1 took place 80 Mya. It is fusogenic, expressed at the syncytialized placental maternofetal interface, and conserved among all carnivorans, consistent with their shared endotheliochorial placenta. Hyenas are a remarkable exception, with a highly invasive hemochorial...

    Mathis Funk, Guillaume Cornelis, Cécile Vernochet, Odile Heidmann, Anne Dupressoir, Alan Conley, Stephen Glickman, Thierry Heidmann
  • Predicting Intraserotypic Recombination in Enterovirus 71
    Genetic Diversity and Evolution
    Predicting Intraserotypic Recombination in Enterovirus 71

    Recombination is a mechanism that contributes to genetic diversity. We describe the first assay to study EV-A71 recombination. Results from this assay mimic what is observed in nature and can be used by others to predict future recombination events within the enterovirus species A group. In addition, our results highlight the central role played by the viral RNA-dependent RNA polymerase (RdRp) in the recombination process. Further, our...

    Andrew Woodman, Kuo-Ming Lee, Richard Janissen, Yu-Nong Gong, Nynke H. Dekker, Shin-Ru Shih, Craig E. Cameron

Virus-Cell Interactions

  • Vectorial Release of Hepatitis E Virus in Polarized Human Hepatocytes
    Virus-Cell Interactions
    Vectorial Release of Hepatitis E Virus in Polarized Human Hepatocytes

    Hepatitis E virus (HEV) in stools is naked, while that in culture supernatants and patients’ blood is lipid associated. Its life cycle in hepatocytes, polarized cells with a basolateral side communicating with blood and an apical side connected with bile, is incompletely understood. We have developed a polarized hepatocyte model and used the cells to analyze the supernatants bathing the apical and basolateral sides and HEV subcellular...

    Nicolas Capelli, Olivier Marion, Martine Dubois, Sophie Allart, Justine Bertrand-Michel, Sébastien Lhomme, Florence Abravanel, Jacques Izopet, Sabine Chapuy-Regaud
  • Cellular RNA Helicase DHX9 Interacts with the Essential Epstein-Barr Virus (EBV) Protein SM and Restricts EBV Lytic Replication
    Virus-Cell Interactions
    Cellular RNA Helicase DHX9 Interacts with the Essential Epstein-Barr Virus (EBV) Protein SM and Restricts EBV Lytic Replication

    This study identifies an interaction between Epstein-Barr virus (EBV) SM protein and cellular helicase DHX9, exploring the roles that this interaction plays in viral infection and host defenses. Whereas most previous studies established DHX9 as a proviral factor, we demonstrate that DHX9 may act as an inhibitor of EBV virion production. DHX9 enhanced innate antiviral pathways active against EBV and was needed for maximal expression of...

    Wenmin Fu, Dinesh Verma, Ashlee Burton, Sankar Swaminathan
  • RNA Helicase A Is an Important Host Factor Involved in Dengue Virus Replication
    Virus-Cell Interactions
    RNA Helicase A Is an Important Host Factor Involved in Dengue Virus Replication

    Dengue, caused by dengue virus, is a rapidly spreading disease, and currently there are no treatments available. Host factors involved in the viral replication of dengue virus are potential antiviral therapeutic targets. Although RHA has been shown to promote the multiplication of several viruses, such as HIV and adenovirus, its role in the flavivirus family, including dengue virus, Japanese encephalitis virus, and emerging Zika virus,...

    Yi Wang, Xiaoyan Chen, Jiong Xie, Shili Zhou, Yanxia Huang, Yi-Ping Li, Xiaobo Li, Chao Liu, Junfang He, Ping Zhang
  • Open Access
    Spatiotemporal Differences in Presentation of CD8 T Cell Epitopes during Hepatitis B Virus Infection
    Virus-Cell Interactions
    Spatiotemporal Differences in Presentation of CD8 T Cell Epitopes during Hepatitis B Virus Infection

    The inability of patients with chronic HBV infection to clear HBV is associated with defective HBV-specific CD8+ T cells. Hence, the majority of immunotherapy developments focus on HBV-specific T cell function restoration. However, knowledge of whether distinct HBV-specific T cells can equally target all the HBV-infected hepatocytes of a chronically infected liver is lacking. In this work, analysis of CHB patient liver...

    Atefeh Khakpoor, Yi Ni, Antony Chen, Zi Zong Ho, Vincent Oei, Ninghan Yang, Reshmi Giri, Jia Xin Chow, Anthony T. Tan, Patrick T. Kennedy, Mala Maini, Stephan Urban, Antonio Bertoletti
  • Defective Viral Genomes Alter How Sendai Virus Interacts with Cellular Trafficking Machinery, Leading to Heterogeneity in the Production of Viral Particles among Infected Cells
    Virus-Cell Interactions | Spotlight
    Defective Viral Genomes Alter How Sendai Virus Interacts with Cellular Trafficking Machinery, Leading to Heterogeneity in the Production of Viral Particles among Infected Cells

    Defective viral genomes (DVGs) generated during Sendai virus infections accumulate in the cytoplasm of some infected cells and stimulate antiviral immunity and cell survival. DVGs are packaged and released as defective particles and have a significant impact on infection outcome. We show that the subpopulation of DVG-high cells poorly engages the virus packaging and budding machinery and do not effectively produce viral particles. In...

    Emmanuelle Genoyer, Carolina B. López
  • Analysis of a Subacute Sclerosing Panencephalitis Genotype B3 Virus from the 2009-2010 South African Measles Epidemic Shows That Hyperfusogenic F Proteins Contribute to Measles Virus Infection in the Brain
    Virus-Cell Interactions
    Analysis of a Subacute Sclerosing Panencephalitis Genotype B3 Virus from the 2009-2010 South African Measles Epidemic Shows That Hyperfusogenic F Proteins Contribute to Measles Virus Infection in the Brain

    Measles virus can invade the central nervous system (CNS) and cause severe neurological complications, such as MIBE and SSPE. However, mechanisms by which MeV enters the CNS and triggers the disease remain unclear. We analyzed viruses from brain tissue of individuals with MIBE or SSPE, infected during the same epidemic, after the onset of neurological disease. Our findings indicate that the emergence of hyperfusogenic MeV F proteins is...

    Fabrizio Angius, Heidi Smuts, Ksenia Rybkina, Debora Stelitano, Brian Eley, Jo Wilmshurst, Marion Ferren, Alexandre Lalande, Cyrille Mathieu, Anne Moscona, Branka Horvat, Takao Hashiguchi, Matteo Porotto, Diana Hardie
  • The Host DHX9 DExH-Box Helicase Is Recruited to Chikungunya Virus Replication Complexes for Optimal Genomic RNA Translation
    Virus-Cell Interactions
    The Host DHX9 DExH-Box Helicase Is Recruited to Chikungunya Virus Replication Complexes for Optimal Genomic RNA Translation

    The reemergence of chikungunya virus (CHIKV), an alphavirus that is transmitted to humans by Aedes mosquitoes, is a serious global health threat. In the absence of effective antiviral drugs, CHIKV infection has a significant impact on human health, with chronic arthritis being one of the most serious complications. The molecular understanding of host-virus interactions is a prerequisite to the development of targeted...

    Roy Matkovic, Eric Bernard, Simon Fontanel, Patrick Eldin, Nathalie Chazal, Deka Hassan Hersi, Andres Merits, Jean-Marie Péloponèse, Laurence Briant
  • Open Access
    Early Porcine Sapovirus Infection Disrupts Tight Junctions and Uses Occludin as a Coreceptor
    Virus-Cell Interactions
    Early Porcine Sapovirus Infection Disrupts Tight Junctions and Uses Occludin as a Coreceptor

    Sapoviruses (SaVs) cause severe acute gastroenteritis in humans and animals. Although they replicate in intestinal epithelial cells, which are tightly sealed by apical-junctional complexes, such as tight junctions (TJs), the mechanisms by which SaVs hijack TJs and their proteins for successful entry and infection remain largely unknown. Here, we demonstrate that porcine SaVs (PSaVs) induce early dissociation of TJs, allowing them to...

    Mia Madel Alfajaro, Eun-Hyo Cho, Deok-Song Kim, Ji-Yun Kim, Jun-Gyu Park, Mahmoud Soliman, Yeong-Bin Baek, Chul-Ho Park, Mun-Il Kang, Sang-Ik Park, Kyoung-Oh Cho
  • Open Access
    Cell Cycle Arrest in G<sub>2</sub>/M Phase Enhances Replication of Interferon-Sensitive Cytoplasmic RNA Viruses via Inhibition of Antiviral Gene Expression
    Virus-Cell Interactions
    Cell Cycle Arrest in G2/M Phase Enhances Replication of Interferon-Sensitive Cytoplasmic RNA Viruses via Inhibition of Antiviral Gene Expression

    Vesicular stomatitis virus (VSV) (a rhabdovirus) and its variant VSV-ΔM51 are widely used model systems to study mechanisms of virus-host interactions. Here, we investigated how the cell cycle affects replication of VSV and VSV-ΔM51. We show that G2/M cell cycle arrest strongly enhances the replication of VSV-ΔM51 (but not of wild-type VSV) and Sendai virus (a paramyxovirus) via inhibition of antiviral gene expression, likely...

    Christian Bressy, Gaith N. Droby, Bryant D. Maldonado, Nury Steuerwald, Valery Z. Grdzelishvili
  • Open Access
    HDAC6 Restricts Influenza A Virus by Deacetylation of the RNA Polymerase PA Subunit
    Virus-Cell Interactions
    HDAC6 Restricts Influenza A Virus by Deacetylation of the RNA Polymerase PA Subunit

    Influenza A virus (IAV) continues to threaten global public health due to drug resistance and the emergence of frequently mutated strains. Thus, it is critical to find new strategies to control IAV infection. Here, we discover one host protein, HDAC6, that can inhibit viral RNA polymerase activity by deacetylating PA and thus suppresses virus RNA replication and transcription. Previously, it was reported that IAV can utilize the HDAC6-...

    Huan Chen, Yingjuan Qian, Xin Chen, Zhiyang Ruan, Yuetian Ye, Hongjun Chen, Lorne A. Babiuk, Yong-Sam Jung, Jianjun Dai
  • Open Access
    Mapping the pH Sensors Critical for Host Cell Entry by a Complex Nonenveloped Virus
    Virus-Cell Interactions
    Mapping the pH Sensors Critical for Host Cell Entry by a Complex Nonenveloped Virus

    Virus entry into a susceptible cell is the first step of infection and a significant point at which infection can be prevented. To enter effectively, viruses must sense the cellular environment and, when appropriate, initiate a series of changes that eventually jettison the protective shell and deposit virus genes into the cytoplasm. Many viruses sense pH, but how this happens and the events that follow are often poorly understood. Here...

    Weining Wu, Cristina C. Celma, Adeline Kerviel, Polly Roy
  • Hepatitis C Virus Escape Studies of Human Antibody AR3A Reveal a High Barrier to Resistance and Novel Insights on Viral Antibody Evasion Mechanisms
    Virus-Cell Interactions
    Hepatitis C Virus Escape Studies of Human Antibody AR3A Reveal a High Barrier to Resistance and Novel Insights on Viral Antibody Evasion Mechanisms

    Hepatitis C virus (HCV) is a leading cause of liver-related mortality, and limited treatment accessibility makes vaccine development a high priority. The vaccine-relevant cross-genotype-reactive antibody AR3A has shown high potency, but the ability of the virus to rapidly escape by mutating the AR3A epitope (barrier to resistance) remains unexplored. Here, we succeeded in inducing only low-level AR3A resistance, indicating a higher...

    Rodrigo Velázquez-Moctezuma, Andrea Galli, Mansun Law, Jens Bukh, Jannick Prentoe
  • Inhibition of DNA-Sensing Pathway by Marek's Disease Virus VP23 Protein through Suppression of Interferon Regulatory Factor 7 Activation
    Virus-Cell Interactions
    Inhibition of DNA-Sensing Pathway by Marek's Disease Virus VP23 Protein through Suppression of Interferon Regulatory Factor 7 Activation

    Despite widespread vaccination, Marek’s disease (MD) continues to pose major challenges for the poultry industry worldwide. MDV causes immunosuppression and deadly lymphomas in chickens, suggesting that this virus has developed a successful immune evasion strategy. However, little is known regarding the initiation and modulation of the host innate immune response during MDV infection. This study demonstrates that the cGAS-STING DNA-...

    Li Gao, Kai Li, Yu Zhang, Yongzhen Liu, Changjun Liu, Yanping Zhang, Yulong Gao, Xiaole Qi, Hongyu Cui, Yongqiang Wang, Xiaomei Wang
  • Autophagy Promotes Replication of Influenza A Virus <em>In Vitro</em>
    Virus-Cell Interactions
    Autophagy Promotes Replication of Influenza A Virus In Vitro

    Autophagy impacts the replication cycle of many viruses. However, the role of the autophagy machinery in IAV replication remains unclear. Therefore, we explored the detailed mechanisms utilized by IAV to promote its replication. We demonstrated that IAV NP- and M2-mediated autophagy promotes IAV replication by regulating the AKT-mTOR signaling pathway and HSP90AA1 expression. The interaction of PB2 and HSP90AA1 results in the increase...

    Ruifang Wang, Yinxing Zhu, Jiachang Zhao, Chenwei Ren, Peng Li, Huanchun Chen, Meilin Jin, Hongbo Zhou
  • The Dengue Virus Nonstructural Protein 1 (NS1) Is Secreted from Mosquito Cells in Association with the Intracellular Cholesterol Transporter Chaperone Caveolin Complex
    Virus-Cell Interactions
    The Dengue Virus Nonstructural Protein 1 (NS1) Is Secreted from Mosquito Cells in Association with the Intracellular Cholesterol Transporter Chaperone Caveolin Complex

    The dengue virus protein NS1 is secreted efficiently from both infected vertebrate and mosquito cells. Previously, our group reported that NS1 secretion in mosquito cells follows an unconventional secretion pathway dependent on caveolin-1. In this work, we demonstrate that in mosquito cells, but not in vertebrate cells, NS1 secretion takes place in association with the chaperone caveolin complex, a complex formed by caveolin-1 and the...

    Romel Rosales Ramirez, Juan E. Ludert
  • Novel Mutations in nsP2 Abolish Chikungunya Virus-Induced Transcriptional Shutoff and Make the Virus Less Cytopathic without Affecting Its Replication Rates
    Virus-Cell Interactions
    Novel Mutations in nsP2 Abolish Chikungunya Virus-Induced Transcriptional Shutoff and Make the Virus Less Cytopathic without Affecting Its Replication Rates

    Chikungunya virus is an important human pathogen which now circulates in both the Old and New Worlds. As in the case of other Old World alphaviruses, CHIKV nsP2 not only has enzymatic functions in viral RNA replication but also is a critical inhibitor of the antiviral response and one of the determinants of CHIKV pathogenesis. In this study, we have applied a new strategy to select a variety of CHIKV nsP2 mutants that no longer...

    Ivan Akhrymuk, Tetyana Lukash, Ilya Frolov, Elena I. Frolova

Cellular Response to Infection

  • Human Papillomavirus 16 E2 Regulates Keratinocyte Gene Expression Relevant to Cancer and the Viral Life Cycle
    Cellular Response to Infection
    Human Papillomavirus 16 E2 Regulates Keratinocyte Gene Expression Relevant to Cancer and the Viral Life Cycle

    Human papillomavirus 16 (HPV16)-positive tumors that retain expression of E2 have a better clinical outcome than those that have lost E2 expression. It has been suggested that this is due to a loss of E2 repression of E6 and E7 expression, but this is not supported by data from tumors where there is not more E6 and E7 expression in the absence of E2. Here we report that E2 regulates host gene expression and place this regulation in the...

    Michael R. Evans, Claire D. James, Molly L. Bristol, Tara J. Nulton, Xu Wang, Namsimar Kaur, Elizabeth A. White, Brad Windle, Iain M. Morgan

Transformation and Oncogenesis

  • Oncogenic Kaposi’s Sarcoma-Associated Herpesvirus Upregulates Argininosuccinate Synthase 1, a Rate-Limiting Enzyme of the Citrulline-Nitric Oxide Cycle, To Activate the STAT3 Pathway and Promote Growth Transformation
    Transformation and Oncogenesis
    Oncogenic Kaposi’s Sarcoma-Associated Herpesvirus Upregulates Argininosuccinate Synthase 1, a Rate-Limiting Enzyme of the Citrulline-Nitric Oxide Cycle, To Activate the STAT3 Pathway and Promote Growth Transformation

    We have previously shown that Kaposi’s sarcoma-associated herpesvirus (KSHV)-transformed cells depend on glutamine rather than glucose for energy production and amino acid and nucleotide syntheses. In this study, we have further examined how the KSHV-reprogramed metabolic pathways are regulated and discovered that KSHV hijacks the citrulline-nitric oxide (NO) cycle to promote growth proliferation and transformation. Multiple KSHV-...

    Tingting Li, Ying Zhu, Fan Cheng, Chun Lu, Jae U. Jung, Shou-Jiang Gao

Gene Delivery

  • Development of Stable Rotavirus Reporter Expression Systems
    Gene Delivery
    Development of Stable Rotavirus Reporter Expression Systems

    Development of reporter RVs has been hampered by the lack of comprehensive reverse genetics systems. Recently, we developed a plasmid-based reverse genetics system that enables generation of reporter RVs expressing NLuc luciferase. The prototype reporter RV had some disadvantages (i.e., the transgene was unstable and was expressed as a fusion protein with a partial NSP1 peptide); however, the improved reporter RV overcomes these...

    Yuta Kanai, Takahiro Kawagishi, Ryotaro Nouda, Misa Onishi, Pimfhun Pannacha, Jeffery A. Nurdin, Keiichiro Nomura, Yoshiharu Matsuura, Takeshi Kobayashi

Vaccines and Antiviral Agents

  • Neutralization Synergy between HIV-1 Attachment Inhibitor Fostemsavir and Anti-CD4 Binding Site Broadly Neutralizing Antibodies against HIV
    Vaccines and Antiviral Agents
    Neutralization Synergy between HIV-1 Attachment Inhibitor Fostemsavir and Anti-CD4 Binding Site Broadly Neutralizing Antibodies against HIV

    As the worldwide HIV pandemic continues, there is a continued need for novel drugs and therapies. A new class of drug, the attachment inhibitors, will soon be approved for the treatment of HIV. Broadly neutralizing antibodies are also promising candidates for HIV prevention and therapy. We investigated how this drug might work with these exciting antibodies that are very potent in blocking HIV infection of cells. These antibodies worked...

    Yijun Zhang, James H. Chapman, Asim Ulcay, Richard E. Sutton
  • An HIV-1 Broadly Neutralizing Antibody from a Clade C-Infected Pediatric Elite Neutralizer Potently Neutralizes the Contemporaneous and Autologous Evolving Viruses
    Vaccines and Antiviral Agents
    An HIV-1 Broadly Neutralizing Antibody from a Clade C-Infected Pediatric Elite Neutralizer Potently Neutralizes the Contemporaneous and Autologous Evolving Viruses

    More than 50% of the HIV-1 infections globally are caused by clade C viruses. To date, there is no effective vaccine to prevent HIV-1 infection. Based on the structural information of the currently available HIV-1 bNAbs, attempts are under way to design immunogens that can elicit correlates of protection upon vaccination. Here, we report the isolation and characterization of an HIV-1 N332 supersite-dependent bNAb, AIIMS-P01, from a...

    Sanjeev Kumar, Harekrushna Panda, Muzamil Ashraf Makhdoomi, Nitesh Mishra, Haaris Ahsan Safdari, Himanshi Chawla, Heena Aggarwal, Elluri Seetharami Reddy, Rakesh Lodha, Sushil Kumar Kabra, Anmol Chandele, Somnath Dutta, Kalpana Luthra
  • Hemagglutinin Stalk-Reactive Antibodies Interfere with Influenza Virus Neuraminidase Activity by Steric Hindrance
    Vaccines and Antiviral Agents | Spotlight
    Hemagglutinin Stalk-Reactive Antibodies Interfere with Influenza Virus Neuraminidase Activity by Steric Hindrance

    This study reports a new mechanism of protection mediated by influenza hemagglutinin stalk-reactive antibodies, i.e., inhibition of neuraminidase activity by steric hindrance, blocking access of neuraminidase to sialic acids when it abuts hemagglutinin on whole virions.

    Yao-Qing Chen, Linda Yu-Ling Lan, Min Huang, Carole Henry, Patrick C. Wilson
  • A 2.8-Angstrom-Resolution Cryo-Electron Microscopy Structure of Human Parechovirus 3 in Complex with Fab from a Neutralizing Antibody
    Vaccines and Antiviral Agents | Spotlight
    A 2.8-Angstrom-Resolution Cryo-Electron Microscopy Structure of Human Parechovirus 3 in Complex with Fab from a Neutralizing Antibody

    Human parechovirus 3 (HPeV3) is receiving increasing attention as a prevalent cause of sepsis-like symptoms in neonates, for which, despite the severity of disease, there are no effective treatments available. Structural and molecular insights into virus neutralization are urgently needed, especially as clinical cases are on the rise. Toward this goal, we present the first structure of HPeV3 in complex with fragments from a neutralizing...

    Aušra Domanska, Justin W. Flatt, Joonas J. J. Jukonen, James A. Geraets, Sarah J. Butcher
  • Closing and Opening Holes in the Glycan Shield of HIV-1 Envelope Glycoprotein SOSIP Trimers Can Redirect the Neutralizing Antibody Response to the Newly Unmasked Epitopes
    Vaccines and Antiviral Agents
    Closing and Opening Holes in the Glycan Shield of HIV-1 Envelope Glycoprotein SOSIP Trimers Can Redirect the Neutralizing Antibody Response to the Newly Unmasked Epitopes

    Engineered SOSIP trimers mimic envelope-glycoprotein spikes, which stud the surface of HIV-1 particles and mediate viral entry into cells. When used for immunizing test animals, they elicit antibodies that neutralize resistant sequence-matched HIV-1 isolates. These neutralizing antibodies recognize epitopes in holes in the glycan shield that covers the trimer. Here, we added glycans to block the most immunogenic neutralization epitopes...

    Rajesh P. Ringe, Pavel Pugach, Christopher A. Cottrell, Celia C. LaBranche, Gemma E. Seabright, Thomas J. Ketas, Gabriel Ozorowski, Sonu Kumar, Anna Schorcht, Marit J. van Gils, Max Crispin, David C. Montefiori, Ian A. Wilson, Andrew B. Ward, Rogier W. Sanders, P. J. Klasse, John P. Moore
  • Verdinexor (KPT-335), a Selective Inhibitor of Nuclear Export, Reduces Respiratory Syncytial Virus Replication <em>In Vitro</em>
    Vaccines and Antiviral Agents
    Verdinexor (KPT-335), a Selective Inhibitor of Nuclear Export, Reduces Respiratory Syncytial Virus Replication In Vitro

    RSV is an important cause of LRTI in infants and young children for which there are no suitable antiviral drugs offered. We evaluated the efficacy of KPT-335 as an anti-RSV drug and show that KPT-335 inhibits XPO1-mediated nuclear export, leading to nuclear accumulation of RSV M protein and reduction in RSV levels. KPT-335 treatment also resulted in inhibition of proinflammatory pathways, which has important implications for its...

    Patricia A. Jorquera, Cynthia Mathew, Jennifer Pickens, Colin Williams, Jasmina M. Luczo, Sharon Tamir, Reena Ghildyal, Ralph A. Tripp
  • Antibody-Mediated Protective Mechanisms Induced by a Trivalent Parainfluenza Virus-Vectored Ebolavirus Vaccine
    Vaccines and Antiviral Agents
    Antibody-Mediated Protective Mechanisms Induced by a Trivalent Parainfluenza Virus-Vectored Ebolavirus Vaccine

    The symptoms of the disease caused by the ebolaviruses Ebola, Bundibugyo, and Sudan are similar, and their areas of endemicity overlap. However, because of the limited antigenic relatedness of the ebolavirus glycoprotein (GP) used in all candidate vaccines against these viruses, they protect only against homologous and not against heterologous ebolaviruses. Therefore, a broadly specific pan-ebolavirus vaccine is required, and this might...

    J. Brian Kimble, Delphine C. Malherbe, Michelle Meyer, Bronwyn M. Gunn, Marcus M. Karim, Philipp A. Ilinykh, Mathieu Iampietro, Khaled S. Mohamed, Surendra Negi, Pavlo Gilchuk, Kai Huang, Yuri I. Wolf, Werner Braun, James E. Crowe, Galit Alter, Alexander Bukreyev
  • Unique Type I Interferon, Expansion/Survival Cytokines, and JAK/STAT Gene Signatures of Multifunctional Herpes Simplex Virus-Specific Effector Memory CD8<sup>+</sup> T<sub>EM</sub> Cells Are Associated with Asymptomatic Herpes in Humans
    Vaccines and Antiviral Agents
    Unique Type I Interferon, Expansion/Survival Cytokines, and JAK/STAT Gene Signatures of Multifunctional Herpes Simplex Virus-Specific Effector Memory CD8+ TEM Cells Are Associated with Asymptomatic Herpes in Humans

    A staggering number of the world population harbors herpes simplex virus 1 (HSV-1) potentially leading to blinding recurrent herpetic disease. While the majority are asymptomatic (ASYMP) individuals who never experienced any recurrent herpetic disease, symptomatic (SYMP) individuals have a history of numerous episodes of recurrent ocular herpetic disease. This study elucidates the phenotype, the effector function, and the gene...

    Hawa Vahed, Anshu Agrawal, Ruchi Srivastava, Swayam Prakash, Pierre-Gregoire A. Coulon, Soumyabrata Roy, Lbachir BenMohamed
  • A Nanobody Targeting Viral Nonstructural Protein 9 Inhibits Porcine Reproductive and Respiratory Syndrome Virus Replication
    Vaccines and Antiviral Agents
    A Nanobody Targeting Viral Nonstructural Protein 9 Inhibits Porcine Reproductive and Respiratory Syndrome Virus Replication

    The pandemic outbreak of PRRS, which is caused by PRRSV, has greatly affected the swine industry. We still lack an efficient vaccine, and it is an immense challenge to control its infection. An intracellularly expressed Nsp9-specific nanobody, Nb6, has been shown to be able to inhibit PRRSV replication in MARC-145 cells. However, its application is limited, because Nb6 cannot physically enter cells. Here, we demonstrated that the cell-...

    Lizhen Wang, Lu Zhang, Baichen Huang, Kuokuo Li, Gaopeng Hou, Qin Zhao, Chunyan Wu, Yuchen Nan, Taofeng Du, Yang Mu, Jixun Lan, Hongying Chen, En-Min Zhou
  • Efficient Inhibition of Avian and Seasonal Influenza A Viruses by a Virus-Specific Dicer-Substrate Small Interfering RNA Swarm in Human Monocyte-Derived Macrophages and Dendritic Cells
    Vaccines and Antiviral Agents
    Efficient Inhibition of Avian and Seasonal Influenza A Viruses by a Virus-Specific Dicer-Substrate Small Interfering RNA Swarm in Human Monocyte-Derived Macrophages and Dendritic Cells

    In spite of the enormous amount of research, influenza virus is still one of the major challenges for medical virology due to its capacity to generate new variants, which potentially lead to severe epidemics and pandemics. We demonstrated here that a swarm of small interfering RNA (siRNA) molecules, including more than 100 different antiviral RNA molecules targeting the most conserved regions of the influenza A virus genome, could...

    Miao Jiang, Pamela Österlund, Veera Westenius, Deyin Guo, Minna M. Poranen, Dennis H. Bamford, Ilkka Julkunen

Pathogenesis and Immunity

  • Functional Analysis and Antivirulence Properties of a New Depolymerase from a Myovirus That Infects <span class="named-content genus-species" id="named-content-1">Acinetobacter baumannii</span> Capsule K45
    Pathogenesis and Immunity
    Functional Analysis and Antivirulence Properties of a New Depolymerase from a Myovirus That Infects Acinetobacter baumannii Capsule K45

    Currently, phage therapy has revived interest for controlling hard-to-treat bacterial infections. Acinetobacter baumannii is an emerging Gram-negative pathogen able to cause a variety of nosocomial infections. Additionally, this species is becoming more resistant to several classes of antibiotics. Here we describe the isolation of a novel lytic myophage B9 and its...

    Hugo Oliveira, Ana Rita Costa, Alice Ferreira, Nico Konstantinides, Sílvio B. Santos, Maarten Boon, Jean-Paul Noben, Rob Lavigne, Joana Azeredo
  • Open Access
    Mechanisms of Abrupt Loss of Virus Control in a Cohort of Previous HIV Controllers
    Pathogenesis and Immunity
    Mechanisms of Abrupt Loss of Virus Control in a Cohort of Previous HIV Controllers

    A few individuals can control HIV infection without the need for antiretroviral treatment and are referred to as HIV controllers. We have studied HIV controllers who suddenly lose this ability and present with high in vivo viral replication and decays in their CD4+ T-cell counts to identify potential immune and virological factors that were responsible for initial virus control. We identify in vitro-...

    Miriam Rosás-Umbert, Anuska Llano, Rocío Bellido, Alex Olvera, Marta Ruiz-Riol, Muntsa Rocafort, Marco A. Fernández, Patricia Cobarsi, Manel Crespo, Lucy Dorrell, Jorge del Romero, José Alcami, Roger Paredes, Christian Brander, Beatriz Mothe
  • Early T Follicular Helper Cell Responses and Germinal Center Reactions Are Associated with Viremia Control in Immunized Rhesus Macaques
    Pathogenesis and Immunity
    Early T Follicular Helper Cell Responses and Germinal Center Reactions Are Associated with Viremia Control in Immunized Rhesus Macaques

    The modest HIV protection observed in the human RV144 vaccine trial associated antibody responses with vaccine efficacy. T follicular helper (TFH) cells are CD4+ T cells that select antibody secreting cells with high antigenic affinity in germinal centers (GCs) within secondary lymphoid organs. To evaluate the role of TFH cells in eliciting prolonged virus-specific humoral responses, we vaccinated rhesus...

    Sabrina Helmold Hait, Diego A. Vargas-Inchaustegui, Thomas Musich, Venkatramanan Mohanram, Iskra Tuero, David J. Venzon, Jenifer Bear, Margherita Rosati, Monica Vaccari, Genoveffa Franchini, Barbara K. Felber, George N. Pavlakis, Marjorie Robert-Guroff
  • Increased Frequency of Virus Shedding by Herpes Simplex Virus 2-Infected Guinea Pigs in the Absence of CD4<sup>+</sup> T Lymphocytes
    Pathogenesis and Immunity
    Increased Frequency of Virus Shedding by Herpes Simplex Virus 2-Infected Guinea Pigs in the Absence of CD4+ T Lymphocytes

    Sexual transmission of HSV-2 results from viral shedding following reactivation from latency. The immune cell populations and mechanisms that control HSV-2 shedding are not well understood. This study examined the role of CD4+ T cells in control of virus shedding using a guinea pig model of genital HSV-2 infection that recapitulates the shedding of virus experienced by humans. We found that the frequency of virus-shedding...

    Nigel Bourne, Clarice L. Perry, Brianne N. Banasik, Aaron L. Miller, Mellodee White, Richard B. Pyles, Hubert Schäfer, Gregg N. Milligan
  • Histidine-Rich Glycoprotein Inhibits HIV-1 Infection in a pH-Dependent Manner
    Pathogenesis and Immunity
    Histidine-Rich Glycoprotein Inhibits HIV-1 Infection in a pH-Dependent Manner

    Vaginal intercourse represents a high-risk route for HIV-1 transmission. The efficiency of male-to-female HIV-1 transmission has been estimated to be 1 in every 1,000 episodes of sexual intercourse, reflecting the high degree of protection conferred by the genital mucosa. However, the contribution of different host factors to the protection against HIV-1 at mucosal surfaces remains poorly defined. Here, we report for the first time that...

    Ezequiel Dantas, Fernando Erra Díaz, Pehuén Pereyra Gerber, Augusto Varese, Diana Alicia Jerusalinsky, Alberto L. Epstein, Hernán J. García Rivello, Ana del Valle Jaén, Julieta B. Pandolfi, Ana Ceballos, Matias Ostrowski, Juan Sabatté, Jorge Geffner
  • A Human Gain-of-Function STING Mutation Causes Immunodeficiency and Gammaherpesvirus-Induced Pulmonary Fibrosis in Mice
    Pathogenesis and Immunity | Spotlight
    A Human Gain-of-Function STING Mutation Causes Immunodeficiency and Gammaherpesvirus-Induced Pulmonary Fibrosis in Mice

    A variety of human rheumatologic disease-causing mutations have recently been identified. Some of these mutations are found in viral nucleic acid-sensing proteins, but whether viruses can influence the onset or progression of these human diseases is less well understood. One such autoinflammatory disease, called STING-associated vasculopathy with onset in infancy (SAVI), affects children and leads to severe lung disease. We generated...

    Brock G. Bennion, Harshad Ingle, Teresa L. Ai, Cathrine A. Miner, Derek J. Platt, Amber M. Smith, Megan T. Baldridge, Jonathan J. Miner
  • Open Access
    Genetic Compatibility of Reassortants between Avian H5N1 and H9N2 Influenza Viruses with Higher Pathogenicity in Mammals
    Pathogenesis and Immunity
    Genetic Compatibility of Reassortants between Avian H5N1 and H9N2 Influenza Viruses with Higher Pathogenicity in Mammals

    Close interaction between avian influenza (AI) viruses and humans in Egypt appears to have resulted in many of the worldwide cases of human infections by both H5N1 and H9N2 AI viruses. Egypt is regarded as a hot spot of AI virus evolution. Although no natural reassortant of H5N1 and H9N2 AI viruses has been reported so far, their cocirculation in Egypt may allow emergence of reassortants that may present a significant public health risk...

    Yasuha Arai, Madiha S. Ibrahim, Emad M. Elgendy, Tomo Daidoji, Takao Ono, Yasuo Suzuki, Takaaki Nakaya, Kazuhiko Matsumoto, Yohei Watanabe
  • Induction of Porcine Dermatitis and Nephropathy Syndrome in Piglets by Infection with Porcine Circovirus Type 3
    Pathogenesis and Immunity
    Induction of Porcine Dermatitis and Nephropathy Syndrome in Piglets by Infection with Porcine Circovirus Type 3

    Porcine circovirus type 3 (PCV3), an emerging porcine circovirus, is considered the cause of porcine dermatitis and nephropathy syndrome (PDNS)-like clinical signs and other systemic diseases in piglets and sows. To evaluate the pathogenesis of PCV3 infection in vivo, we used a PCV3 virus stock from the rescue of an infectious PCV3 DNA clone to intranasally inoculate 4- and 8-week-old specific-pathogen-free piglets and...

    Haijun Jiang, Dan Wang, Jing Wang, Shanshan Zhu, Ruiping She, Xinxin Ren, Jijing Tian, Rong Quan, Lei Hou, Zixuan Li, Jun Chu, Yuxin Guo, Yanyang Xi, Huiqi Song, Feng Yuan, Li Wei, Jue Liu
  • Identification and Functional Characterization of a Novel Fc Gamma-Binding Glycoprotein in Rhesus Cytomegalovirus
    Pathogenesis and Immunity
    Identification and Functional Characterization of a Novel Fc Gamma-Binding Glycoprotein in Rhesus Cytomegalovirus

    Rhesus cytomegalovirus (RhCMV) offers a unique model for studying human cytomegalovirus (HCMV) pathogenesis and vaccine development. RhCMV infection of nonhuman primates greatly broadened the understanding of mechanisms by which CMVs evade or reprogram T cell and natural killer cell responses in vivo. However, the role of humoral immunity and viral modulation of anti-CMV antibodies has not been studied in this model. There is...

    Philipp Kolb, Steven Sijmons, Matthew R. McArdle, Husam Taher, Jennie Womack, Colette Hughes, Abigail Ventura, Michael A. Jarvis, Christiane Stahl-Hennig, Scott Hansen, Louis J. Picker, Daniel Malouli, Hartmut Hengel, Klaus Früh

Author Correction

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    Correction for Cadena-Nava et al., “Self-Assembly of Viral Capsid Protein and RNA Molecules of Different Sizes: Requirement for a Specific High Protein/RNA Mass Ratio”
    Author Correction
    Correction for Cadena-Nava et al., “Self-Assembly of Viral Capsid Protein and RNA Molecules of Different Sizes: Requirement for a Specific High Protein/RNA Mass Ratio”
    Ruben D. Cadena-Nava, Mauricio Comas-Garcia, Rees F. Garmann, A. L. N. Rao, Charles M. Knobler, William M. Gelbart

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Journal of Virology: 93 (4)

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volume 93, issue 4
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  • Receptor Recognition by the Novel Coronavirus from Wuhan: an Analysis Based on Decade-Long Structural Studies of SARS Coronavirus
  • COVID-19 Vaccines: “Warp Speed” Needs Mind Melds, Not Warped Minds
  • Nucleocapsid Protein Recruitment to Replication-Transcription Complexes Plays a Crucial Role in Coronaviral Life Cycle
  • Molecular Mechanism for Antibody-Dependent Enhancement of Coronavirus Entry
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