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Table of Contents

January 2019; Volume 93,Issue 2

Spotlight

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

Gem

  • Free
    Impact of Replication Stress in Human Papillomavirus Pathogenesis
    Gem
    Impact of Replication Stress in Human Papillomavirus Pathogenesis

    The inactivation of critical cell cycle checkpoints by the human papillomavirus (HPV) oncoprotein E7 results in replication stress (RS) that leads to genomic instability in premalignant lesions. Intriguingly, RS tolerance is achieved through several mechanisms, enabling HPV to exploit the cellular RS response for viral replication and to facilitate viral persistence in the presence of DNA damage.

    Cary A. Moody

Structure and Assembly

  • Isolation of Neutralizing Monoclonal Antibodies to Human Astrovirus and Characterization of Virus Variants That Escape Neutralization
    Structure and Assembly
    Isolation of Neutralizing Monoclonal Antibodies to Human Astrovirus and Characterization of Virus Variants That Escape Neutralization

    Human astroviruses (HAstVs) are common etiological agents of acute gastroenteritis in children, the elderly, and immunocompromised patients; some virus strains have also been associated with neurological disease. Despite their medical importance, the study of these pathogens has advanced at a slow pace. In this work, we produced neutralizing antibodies to the virus and mapped the epitopes they recognize on the virus capsid. These...

    Rafaela Espinosa, Tomás López, Walter A. Bogdanoff, Marco A. Espinoza, Susana López, Rebecca M. DuBois, Carlos F. Arias
  • Open Access
    Encapsidation of Viral RNA in <em>Picornavirales</em>: Studies on Cowpea Mosaic Virus Demonstrate Dependence on Viral Replication
    Structure and Assembly
    Encapsidation of Viral RNA in Picornavirales: Studies on Cowpea Mosaic Virus Demonstrate Dependence on Viral Replication

    The mechanism whereby members of the order Picornavirales specifically package their genomic RNAs is poorly understood. Research with monopartite members of the order, such as poliovirus, indicated that packaging is linked to replication, although the presence of “packaging signals” along the length of the viral RNA has also been suggested. Thanks to the bipartite nature of the CPMV genome, which allows the manipulation of RNA-...

    Inga Kruse, Hadrien Peyret, Pooja Saxena, George P. Lomonossoff
  • Structural Basis for Human Norovirus Capsid Binding to Bile Acids
    Structure and Assembly
    Structural Basis for Human Norovirus Capsid Binding to Bile Acids

    Given that human norovirus virions likely interact with bile acid during a natural infection, our evidence that an HBGA nonbinder (GII.1) can be converted to an HBGA binder after bile acid binding is of major significance. Our data provide direct evidence that, like HBGAs, bile acid interaction on the capsid is an important cofactor for certain genotypes. However, more unanswered questions seem to arise from these new discoveries. For...

    Turgay Kilic, Anna Koromyslova, Grant S. Hansman
  • Components of the Reovirus Capsid Differentially Contribute to Stability
    Structure and Assembly
    Components of the Reovirus Capsid Differentially Contribute to Stability

    Nonenveloped and enveloped viruses are exposed to the environment during transmission to a new host. Protein-protein and/or protein-lipid interactions stabilize the particle and protect the viral genome. Mammalian orthoreovirus (reovirus) is composed of two concentric, protein shells. The μ1 and σ3 proteins form the outer capsid; contacts between neighboring subunits are thought to confer resistance to inactivating agents. We further...

    Anthony J. Snyder, Joseph Che-Yen Wang, Pranav Danthi

Genome Replication and Regulation of Viral Gene Expression

  • Inhibition of Epstein-Barr Virus Replication in Human Papillomavirus-Immortalized Keratinocytes
    Genome Replication and Regulation of Viral Gene Expression
    Inhibition of Epstein-Barr Virus Replication in Human Papillomavirus-Immortalized Keratinocytes

    Using a model examining the establishment of EBV infection in HPV-immortalized tissues, we showed an HPV-induced interruption of the normal EBV life cycle reminiscent of a latent EBV infection. Our data support the notion that a persistent EBV epithelial infection depends upon preexisting cellular alterations and suggest the ability of HPV to promote such changes. More importantly, these findings introduce a model for how EBV...

    J. T. Guidry, J. E. Myers, M. Bienkowska-Haba, W. K. Songock, X. Ma, M. Shi, C. O. Nathan, J. M. Bodily, M. J. Sapp, R. S. Scott
  • Minute Virus of Canines NP1 Protein Interacts with the Cellular Factor CPSF6 To Regulate Viral Alternative RNA Processing
    Genome Replication and Regulation of Viral Gene Expression | Spotlight
    Minute Virus of Canines NP1 Protein Interacts with the Cellular Factor CPSF6 To Regulate Viral Alternative RNA Processing

    The Parvovirinae are small nonenveloped icosahedral viruses that are important pathogens in many animal species, including humans. Unlike other parvoviruses, the bocavirus genus controls expression of its capsid proteins via alternative RNA processing, by both suppressing polyadenylation at an internal site, termed the proximal polyadenylation (pA)p site, and by facilitating splicing of an upstream adjacent intron. This...

    Yanming Dong, Olufemi O. Fasina, David J. Pintel
  • A Genome-Wide Epstein-Barr Virus Polyadenylation Map and Its Antisense RNA to EBNA
    Genome Replication and Regulation of Viral Gene Expression
    A Genome-Wide Epstein-Barr Virus Polyadenylation Map and Its Antisense RNA to EBNA

    Epstein-Barr virus represents an important human pathogen with an etiological role in the development of several cancers. By elucidation of a genome-wide polyadenylation landscape of EBV in JSC-1, Raji, and Akata cells, we have redefined the EBV transcriptome and mapped individual polymerase II (Pol II) transcripts of viral genes to each one of the mapped pA sites at single-nucleotide resolution as well as the depth of expression. By...

    Vladimir Majerciak, Wenjing Yang, Jing Zheng, Jun Zhu, Zhi-Ming Zheng
  • Group A Rotavirus VP1 Polymerase and VP2 Core Shell Proteins: Intergenotypic Sequence Variation and <em>In Vitro</em> Functional Compatibility
    Genome Replication and Regulation of Viral Gene Expression
    Group A Rotavirus VP1 Polymerase and VP2 Core Shell Proteins: Intergenotypic Sequence Variation and In Vitro Functional Compatibility

    Group A rotaviruses (RVAs) are widespread in nature, infecting numerous mammalian and avian hosts and causing severe gastroenteritis in human children. RVAs are classified using a system that assigns a genotype to each viral gene according to its nucleotide sequence. To date, 22 genotypes have been described for the gene encoding the viral polymerase (VP1), and 20 genotypes have been described for the gene encoding the core shell...

    Courtney L. Steger, Crystal E. Boudreaux, Leslie E. LaConte, James B. Pease, Sarah M. McDonald

Genetic Diversity and Evolution

  • Open Access
    Metagenomic Sequencing of HIV-1 in the Blood and Female Genital Tract Reveals Little Quasispecies Diversity during Acute Infection
    Genetic Diversity and Evolution
    Metagenomic Sequencing of HIV-1 in the Blood and Female Genital Tract Reveals Little Quasispecies Diversity during Acute Infection

    Due to error-prone replication, HIV-1 generates a diverse population of viruses within a chronically infected individual. When HIV-1 is transmitted to a new individual, one or a few viruses establish the new infection, leading to a genetic bottleneck in the virus population. Understanding the timing and nature of this bottleneck may provide insight into HIV-1 vaccine design and other preventative strategies. We examined the HIV-1...

    Anne Piantadosi, Catherine A. Freije, Christina Gosmann, Simon Ye, Daniel Park, Stephen F. Schaffner, Damien C. Tully, Todd M. Allen, Krista L. Dong, Pardis C. Sabeti, Douglas S. Kwon
  • Eurasian Avian-Like Swine Influenza A Viruses Escape Human MxA Restriction through Distinct Mutations in Their Nucleoprotein
    Genetic Diversity and Evolution | Spotlight
    Eurasian Avian-Like Swine Influenza A Viruses Escape Human MxA Restriction through Distinct Mutations in Their Nucleoprotein

    The human MxA protein efficiently blocks the replication of IAV from nonhuman species. In rare cases, however, these IAV overcome the species barrier and become pandemic. All known pandemic viruses have acquired and maintained MxA escape mutations in the viral NP and thus are not efficiently controlled by MxA. Intriguingly, partial MxA resistance can also be acquired in other hosts that express antivirally active Mx proteins, such as...

    Dominik Dornfeld, Philipp P. Petric, Ebrahim Hassan, Roland Zell, Martin Schwemmle
  • Isolation and Characterization of a Distinct Influenza A Virus from Egyptian Bats
    Genetic Diversity and Evolution
    Isolation and Characterization of a Distinct Influenza A Virus from Egyptian Bats

    Through surveillance, we isolated and characterized an influenza A virus from Egyptian fruit bats. This virus had an affinity to avian-like receptors but was also able to infect mice. Our findings indicate that bats may harbor a diversity of influenza A viruses. Such viruses may have the potential to cross the species barrier to infect other species, including domestic birds, mammals, and, possibly, humans.

    Ahmed Kandeil, Mokhtar R. Gomaa, Mahmoud M. Shehata, Ahmed N. El Taweel, Sara H. Mahmoud, Ola Bagato, Yassmin Moatasim, Omnia Kutkat, Ahmed S. Kayed, Patrick Dawson, Xueting Qiu, Justin Bahl, Richard J. Webby, William B. Karesh, Ghazi Kayali, Mohamed A. Ali
  • Plasticity of Amino Acid Residue 145 Near the Receptor Binding Site of H3 Swine Influenza A Viruses and Its Impact on Receptor Binding and Antibody Recognition
    Genetic Diversity and Evolution
    Plasticity of Amino Acid Residue 145 Near the Receptor Binding Site of H3 Swine Influenza A Viruses and Its Impact on Receptor Binding and Antibody Recognition

    The complex and continuous antigenic evolution of IAVs remains a major hurdle for vaccine selection and effective vaccination. On the hemagglutinin (HA) of the H3N2 IAVs, the amino acid substitution N 145 K causes significant antigenic changes. We show that amino acid 145 displays remarkable amino acid plasticity in vitro, tolerating multiple amino acid substitutions, many of which have not yet been observed in nature. Mutant...

    Jefferson J. S. Santos, Eugenio J. Abente, Adebimpe O. Obadan, Andrew J. Thompson, Lucas Ferreri, Ginger Geiger, Ana S. Gonzalez-Reiche, Nicola S. Lewis, David F. Burke, Daniela S. Rajão, James C. Paulson, Amy L. Vincent, Daniel R. Perez

Virus-Cell Interactions

  • Hepatitis B e Antigen Inhibits NF-κB Activity by Interrupting K63-Linked Ubiquitination of NEMO
    Virus-Cell Interactions | Spotlight
    Hepatitis B e Antigen Inhibits NF-κB Activity by Interrupting K63-Linked Ubiquitination of NEMO

    The role of HBeAg in inflammatory responses during the infection of hepatitis B virus (HBV) is not fully understood, and several previous reports with regard to the NF-κB pathway are controversial. In this study, we showed that HBeAg could suppress both Toll-like receptor 2 (TLR2)- and IL-1β-induced activation of NF-κB in cells and clinical samples, and we further revealed novel molecular mechanisms. We found that HBeAg can associate...

    Yuan Wang, Lei Cui, Guifang Yang, Jianbo Zhan, Liang Guo, Yu Chen, Chengpeng Fan, Dan Liu, Deyin Guo
  • Foot-and-Mouth Disease Virus Leader Protease Cleaves G3BP1 and G3BP2 and Inhibits Stress Granule Formation
    Virus-Cell Interactions
    Foot-and-Mouth Disease Virus Leader Protease Cleaves G3BP1 and G3BP2 and Inhibits Stress Granule Formation

    The picornavirus foot-and-mouth disease virus (FMDV) is a notorious animal pathogen that puts a major economic burden on the global livestock industry. Outbreaks have significant consequences for animal health and product safety. Like many other viruses, FMDV must manipulate antiviral host responses to establish infection. Upon infection, viral double-stranded RNA (dsRNA) is detected, which results in the activation of the RNA-dependent...

    Linda J. Visser, Gisselle N. Medina, Huib H. Rabouw, Raoul J. de Groot, Martijn A. Langereis, Teresa de los Santos, Frank J. M. van Kuppeveld
  • Hepatitis C Virus Downregulates Ubiquitin-Conjugating Enzyme E2S Expression To Prevent Proteasomal Degradation of NS5A, Leading to Host Cells More Sensitive to DNA Damage
    Virus-Cell Interactions
    Hepatitis C Virus Downregulates Ubiquitin-Conjugating Enzyme E2S Expression To Prevent Proteasomal Degradation of NS5A, Leading to Host Cells More Sensitive to DNA Damage

    Protein homeostasis is essential to normal cell function. HCV infection disturbs the protein homeostasis in the host cells. Therefore, host cells exert an anti-HCV activity in order to maintain normal cellular metabolism. We showed that UBE2S interacted with HCV NS5A and degraded NS5A protein through the Lys11-linked proteasome-dependent pathway. However, HCV has evolved to overcome host antiviral activity. We demonstrated that the...

    Hang T. Pham, Tram T. T. Nguyen, Lap P. Nguyen, Sang-Seop Han, Yun-Sook Lim, Soon B. Hwang
  • A MicroRNA Derived from Adenovirus Virus-Associated RNAII Promotes Virus Infection via Posttranscriptional Gene Silencing
    Virus-Cell Interactions
    A MicroRNA Derived from Adenovirus Virus-Associated RNAII Promotes Virus Infection via Posttranscriptional Gene Silencing

    Several types of viruses encode viral miRNAs which regulate host and/or viral gene expression via posttranscriptional gene silencing, leading to efficient viral infection. Adenovirus (Ad) expresses miRNAs derived from VA-RNAs (mivaRNAI and -II); however, recent studies have revealed that processing of VA-RNAI into mivaRNAI inhibits Ad replication. Conversely, we demonstrate here that mivaRNAII significantly promotes Ad replication and...

    K. Wakabayashi, M. Machitani, M. Tachibana, F. Sakurai, H. Mizuguchi
  • Mutations in the Spike Protein of Middle East Respiratory Syndrome Coronavirus Transmitted in Korea Increase Resistance to Antibody-Mediated Neutralization
    Virus-Cell Interactions
    Mutations in the Spike Protein of Middle East Respiratory Syndrome Coronavirus Transmitted in Korea Increase Resistance to Antibody-Mediated Neutralization

    MERS-CoV has pandemic potential, and it is important to identify mutations in viral proteins that might augment viral spread. In the course of a large hospital outbreak of MERS in the Republic of Korea in 2015, the spread of a viral variant that contained mutations in the viral spike protein was observed. These mutations were found to reduce receptor binding and viral infectivity. However, it remained unclear whether they also exerted...

    Hannah Kleine-Weber, Mahmoud Tarek Elzayat, Lingshu Wang, Barney S. Graham, Marcel A. Müller, Christian Drosten, Stefan Pöhlmann, Markus Hoffmann
  • Murine Leukemia Virus Glycosylated Gag Reduces Murine SERINC5 Protein Expression at Steady-State Levels via the Endosome/Lysosome Pathway to Counteract SERINC5 Antiretroviral Activity
    Virus-Cell Interactions
    Murine Leukemia Virus Glycosylated Gag Reduces Murine SERINC5 Protein Expression at Steady-State Levels via the Endosome/Lysosome Pathway to Counteract SERINC5 Antiretroviral Activity

    MLV glycoGag not only enhances MLV replication but also increases HIV-1 infectivity similarly as Nef. Recent studies have discovered that both glycoGag and Nef antagonize a novel host restriction factor Ser5 and promote viral replication. Compared to Nef, the glycoGag antagonism of Ser5 is still poorly understood. MLV glycoGag is a transmembrane version of the structural Gag protein with an extra 88-amino-acid leader region that...

    Sunan Li, Iqbal Ahmad, Jing Shi, Bin Wang, Changqing Yu, Lixin Zhang, Yong-Hui Zheng
  • HIV-1 Antisense Protein of Different Clades Induces Autophagy and Associates with the Autophagy Factor p62
    Virus-Cell Interactions | Spotlight
    HIV-1 Antisense Protein of Different Clades Induces Autophagy and Associates with the Autophagy Factor p62

    In the present study, we provide the first evidence that a new HIV-1 protein termed ASP derived from different clades acts similarly in inducing autophagy, an important cellular process implicated in the degradation of excess or defective cellular material. We have gained further knowledge on the mechanism mediating the activation of autophagy. Our studies have important ramifications in the understanding of viral replication and the...

    Zhenlong Liu, Cynthia Torresilla, Yong Xiao, Phuong Trang Nguyen, Clément Caté, Karina Barbosa, Éric Rassart, Shan Cen, Steve Bourgault, Benoit Barbeau
  • Selective Editing of Herpes Simplex Virus 1 Enables Interferon Induction and Viral Replication That Destroy Malignant Cells
    Virus-Cell Interactions
    Selective Editing of Herpes Simplex Virus 1 Enables Interferon Induction and Viral Replication That Destroy Malignant Cells

    Oncolytic herpes simplex virus 1 is a promising agent for cancer immunotherapy. Due to a complex virus-host interaction, less is clear about what viral signature(s) constitutes a potent oncolytic backbone. Through molecular or genetic dissection, we showed that selective editing of the γ134.5 gene enables viral replication in malignant cells, activation of transcription factor IRF3, and subsequent induction of type I IFN....

    Xing Liu, Bin He
  • The NS1 Protein of Influenza A Virus Participates in Necroptosis by Interacting with MLKL and Increasing Its Oligomerization and Membrane Translocation
    Virus-Cell Interactions
    The NS1 Protein of Influenza A Virus Participates in Necroptosis by Interacting with MLKL and Increasing Its Oligomerization and Membrane Translocation

    Necroptosis is a programmed cell death that is inflammatory in nature owing to the release of danger-associated molecular patterns from the ruptured cell membrane. However, necroptosis also constitutes an important arm of host immune responses. Thus, a balanced inflammatory response determines the disease outcome. We report that the NS1 protein of IAV participates in necroptosis by interacting with MLKL, resulting in increased MLKL...

    Amit Gaba, Fang Xu, Yao Lu, Hong-Su Park, GuanQun Liu, Yan Zhou
  • Low-pH Endocytic Entry of the Porcine Alphaherpesvirus Pseudorabies Virus
    Virus-Cell Interactions
    Low-pH Endocytic Entry of the Porcine Alphaherpesvirus Pseudorabies Virus

    PRV is a pathogen of great economic and animal welfare importance in many parts of the world. PRV causes neurological, respiratory, and reproductive disorders, often resulting in mortality of young and immunocompromised animals. Mortality, decreased production, and trade restrictions result in significant financial losses for the agricultural industry. Understanding the molecular mechanisms utilized by PRV to enter host cells is an...

    Jonathan L. Miller, Darin J. Weed, Becky H. Lee, Suzanne M. Pritchard, Anthony V. Nicola
  • Biogenesis of Extracellular Vesicles during Herpes Simplex Virus 1 Infection: Role of the CD63 Tetraspanin
    Virus-Cell Interactions
    Biogenesis of Extracellular Vesicles during Herpes Simplex Virus 1 Infection: Role of the CD63 Tetraspanin

    Intercellular communication, especially in neurons, largely relies on EVs, and modulation of EVs is known to impact physiological processes. Here, we present evidence that HSV-1 infection causes major alterations in the biogenesis of EVs, including an increase in their number and an increase in the CD63-positive population of EVs. These alterations result in an enrichment of the milieu of infection with EVs carrying signatures from...

    Christos Dogrammatzis, Thibaut Deschamps, Maria Kalamvoki

Cellular Response to Infection

  • Open Access
    Dynamics of Virus-Specific Memory B Cells and Plasmablasts following Viral Infection of the Central Nervous System
    Cellular Response to Infection
    Dynamics of Virus-Specific Memory B Cells and Plasmablasts following Viral Infection of the Central Nervous System

    The prevalence and role of antigen-specific Bmem in the CNS during viral encephalomyelitis is largely undefined. A lack of reliable markers identifying murine Bmem has made it difficult to assess their contribution to local antiviral protection via antigen presentation or conversion to ASC. Using reporter mice infected with neurotropic coronavirus to track virus-specific Bmem and ASC, this report demonstrates that both subsets only...

    Jeffrey R. Atkinson, Mihyun Hwang, Angel Reyes-Rodriguez, Cornelia C. Bergmann
  • Released Tryptophanyl-tRNA Synthetase Stimulates Innate Immune Responses against Viral Infection
    Cellular Response to Infection
    Released Tryptophanyl-tRNA Synthetase Stimulates Innate Immune Responses against Viral Infection

    ARSs are essential enzymes in translation that link specific amino acids to their cognate tRNAs. In higher eukaryotes, some ARSs possess additional, noncanonical functions in the regulation of cell metabolism. Here, we report a novel noncanonical function of WRS in antiviral defense. WRS is rapidly secreted in response to viral infection and primes the innate immune response by inducing the secretion of proinflammatory cytokines and...

    Hyun-Cheol Lee, Eun-Seo Lee, Md Bashir Uddin, Tae-Hwan Kim, Jae-Hoon Kim, Kiramage Chathuranga, W. A. Gayan Chathuranga, Mirim Jin, Sunghoon Kim, Chul-Joong Kim, Jong-Soo Lee
  • Open Access
    DUSP10 Negatively Regulates the Inflammatory Response to Rhinovirus through Interleukin-1β Signaling
    Cellular Response to Infection
    DUSP10 Negatively Regulates the Inflammatory Response to Rhinovirus through Interleukin-1β Signaling

    Rhinoviruses are one of the causes of the common cold. In patients with asthma or chronic obstructive pulmonary disease, viral infections, including those with rhinovirus, are the commonest cause of exacerbations. Novel therapeutics to limit viral inflammation are clearly required. The work presented here identifies DUSP10 as an important protein involved in limiting the inflammatory response in the airway without affecting immune...

    Grace C. A. Manley, Clare A. Stokes, Elizabeth K. Marsh, Ian Sabroe, Lisa C. Parker
  • Functional Mapping of Regions Involved in the Negative Imprinting of Virion Particle Infectivity and in Target Cell Protection by Interferon-Induced Transmembrane Protein 3 against HIV-1
    Cellular Response to Infection
    Functional Mapping of Regions Involved in the Negative Imprinting of Virion Particle Infectivity and in Target Cell Protection by Interferon-Induced Transmembrane Protein 3 against HIV-1

    IFITM proteins have been associated with the sequestration of incoming virions in endosomes (target cell protection) and with the production of virion particles that incorporate IFITMs and exhibit decreased infectivity (negative imprinting of virion infectivity). How the latter is regulated and whether these two antiviral properties are related remain unknown. By examining the behavior of a large panel of IFITM3 mutants against HIV-1,...

    Romain Appourchaux, Mathilde Delpeuch, Li Zhong, Julien Burlaud-Gaillard, Kevin Tartour, George Savidis, Abraham Brass, Lucie Etienne, Philippe Roingeard, Andrea Cimarelli

Vaccines and Antiviral Agents

  • BCL6 Inhibitor-Mediated Downregulation of Phosphorylated SAMHD1 and T Cell Activation Are Associated with Decreased HIV Infection and Reactivation
    Vaccines and Antiviral Agents
    BCL6 Inhibitor-Mediated Downregulation of Phosphorylated SAMHD1 and T Cell Activation Are Associated with Decreased HIV Infection and Reactivation

    The expansion and accumulation of HIV-infected BCL6+ Tfh CD4+ T cells are thought to contribute to the persistence of viral reservoirs in infected subjects undergoing ART. Two mechanisms have been raised for the preferential retention of HIV within Tfh CD4+ T cells: (i) antiretroviral drugs have limited tissue distribution, resulting in insufficient tissue concentration and lower efficacy in controlling...

    Yanhui Cai, Mohamed Abdel-Mohsen, Costin Tomescu, Fengtian Xue, Guoxin Wu, Bonnie J. Howell, Yong Ai, Jie Sun, Livio Azzoni, Carole Le Coz, Neil Romberg, Luis J. Montaner
  • Dolutegravir Monotherapy of Simian Immunodeficiency Virus-Infected Macaques Selects for Several Patterns of Resistance Mutations with Variable Virological Outcomes
    Vaccines and Antiviral Agents
    Dolutegravir Monotherapy of Simian Immunodeficiency Virus-Infected Macaques Selects for Several Patterns of Resistance Mutations with Variable Virological Outcomes

    A growing number of anti-HIV drug combinations are effective in suppressing virus replication in HIV-infected persons. However, to reduce their cost and risk for toxicity, there is considerable interest in simplifying drug regimens. A major concern with single-drug regimens is the emergence of drug-resistant viral mutants. It has been speculated that DTG monotherapy may be a feasible option, because DTG may have a higher genetic barrier...

    Koen K. A. Van Rompay, Said Hassounah, Brandon F. Keele, Jeffrey D. Lifson, Amir Ardeshir, Jennifer Watanabe, Hanh Thi Pham, Elena Chertova, Raymond Sowder, Jan Balzarini, Thibault Mesplède, Mark A. Wainberg
  • Open Access
    Determining the Mutation Bias of Favipiravir in Influenza Virus Using Next-Generation Sequencing
    Vaccines and Antiviral Agents
    Determining the Mutation Bias of Favipiravir in Influenza Virus Using Next-Generation Sequencing

    New antiviral drugs are needed as a first line of defense in the event of a novel influenza pandemic. Favipiravir is a broad-spectrum antiviral which is effective against influenza. The exact mechanism of how favipiravir works to inhibit influenza is still unclear. We used next-generation sequencing (NGS) to demonstrate that favipiravir causes mutations in influenza RNA. The greater depth of NGS sequence information over traditional...

    Daniel H. Goldhill, Pinky Langat, Hongyao Xie, Monica Galiano, Shahjahan Miah, Paul Kellam, Maria Zambon, Angie Lackenby, Wendy S. Barclay
  • Sensitivity to Broadly Neutralizing Antibodies of Recently Transmitted HIV-1 Clade CRF02_AG Viruses with a Focus on Evolution over Time
    Vaccines and Antiviral Agents
    Sensitivity to Broadly Neutralizing Antibodies of Recently Transmitted HIV-1 Clade CRF02_AG Viruses with a Focus on Evolution over Time

    Major progress occurred during the last decade leading to the isolation of human monoclonal antibodies, termed broadly neutralizing antibodies (bnAbs) due to their capacity to neutralize various strains of HIV-1. Several clinical trials are under way in order to evaluate their efficacy in preventive or therapeutic strategies. However, no single bnAb is active against 100% of strains. It is important to gather data on the sensitivity to...

    Karl Stefic, Mélanie Bouvin-Pley, Asma Essat, Clara Visdeloup, Alain Moreau, Cécile Goujard, Marie-Laure Chaix, Martine Braibant, Laurence Meyer, Francis Barin
    and on behalf of the ANRS PRIMO Cohort Study Group
  • Mutations in Influenza A Virus Neuraminidase and Hemagglutinin Confer Resistance against a Broadly Neutralizing Hemagglutinin Stem Antibody
    Vaccines and Antiviral Agents
    Mutations in Influenza A Virus Neuraminidase and Hemagglutinin Confer Resistance against a Broadly Neutralizing Hemagglutinin Stem Antibody

    Influenza A virus is a public health threat for which currently available vaccines are not always effective. Broadly neutralizing antibodies that bind to the highly conserved stem region of the influenza virus hemagglutinin (HA) can neutralize many influenza virus strains. To understand how influenza virus can become resistant or escape such antibodies, we propagated influenza A virus in vitro with escalating concentrations of...

    Kristina L. Prachanronarong, Aneth S. Canale, Ping Liu, Mohan Somasundaran, Shurong Hou, Yu-Ping Poh, Thomas Han, Quan Zhu, Nicholas Renzette, Konstantin B. Zeldovich, Timothy F. Kowalik, Nese Kurt-Yilmaz, Jeffrey D. Jensen, Daniel N. A. Bolon, Wayne A. Marasco, Robert W. Finberg, Celia A. Schiffer, Jennifer P. Wang
  • Antibody Responses toward the Major Antigenic Sites of Influenza B Virus Hemagglutinin in Mice, Ferrets, and Humans
    Vaccines and Antiviral Agents
    Antibody Responses toward the Major Antigenic Sites of Influenza B Virus Hemagglutinin in Mice, Ferrets, and Humans

    This study dissected the specific antibody responses toward the major antigenic sites and the noncanonical epitopes of influenza B virus hemagglutinin in animals and humans using novel reagents. These findings will guide the design of the next generation of influenza virus vaccines.

    Weina Sun, Davina S. Kang, Allen Zheng, Sean T. H. Liu, Felix Broecker, Viviana Simon, Florian Krammer, Peter Palese
  • <em>N</em>-Glycosylation of Seasonal Influenza Vaccine Hemagglutinins: Implication for Potency Testing and Immune Processing
    Vaccines and Antiviral Agents
    N-Glycosylation of Seasonal Influenza Vaccine Hemagglutinins: Implication for Potency Testing and Immune Processing

    In the present study, the glycosylation patterns of the 2014-2015 influenza vaccine season standard antigens A/California/07/2009 H1N1, A/Texas/50/2012 H3N2, and B/Massachusetts/02/2012 were revealed, and the sensitivity of the single radial immunodiffusion (SRID) potency test to glycosylation was tested. Differences in hemagglutinin glycosylation site composition and heterogeneity seen in antigens produced in different cell substrates...

    Yanming An, Lisa M. Parsons, Ewa Jankowska, Darya Melnyk, Manju Joshi, John F. Cipollo

Pathogenesis and Immunity

  • Open Access
    Mutation of Influenza A Virus PA-X Decreases Pathogenicity in Chicken Embryos and Can Increase the Yield of Reassortant Candidate Vaccine Viruses
    Pathogenesis and Immunity
    Mutation of Influenza A Virus PA-X Decreases Pathogenicity in Chicken Embryos and Can Increase the Yield of Reassortant Candidate Vaccine Viruses

    Influenza A virus is a widespread pathogen that affects both humans and a variety of animal species, causing regular epidemics and sporadic pandemics, with major public health and economic consequences. A better understanding of virus biology is therefore important. The primary control measure is vaccination, which for humans mostly relies on antigens produced in eggs from PR8-based viruses bearing the glycoprotein genes of interest....

    Saira Hussain, Matthew L. Turnbull, Helen M. Wise, Brett W. Jagger, Philippa M. Beard, Kristina Kovacikova, Jeffery K. Taubenberger, Lonneke Vervelde, Othmar G. Engelhardt, Paul Digard
  • Open Access
    Acute Infection and Subsequent Subclinical Reactivation of Herpes Simplex Virus 2 after Vaginal Inoculation of Rhesus Macaques
    Pathogenesis and Immunity
    Acute Infection and Subsequent Subclinical Reactivation of Herpes Simplex Virus 2 after Vaginal Inoculation of Rhesus Macaques

    Herpes simplex virus 2 (HSV-2) infects nearly 500 million persons globally, with an estimated 21 million incident cases each year, making it one of the most common sexually transmitted infections (STIs). HSV-2 is associated with increased human immunodeficiency virus type 1 (HIV-1) acquisition, and this risk does not decline with the use of antiherpes drugs. As initial acquisition of both HIV and HSV-2 infections is subclinical, study...

    Ming Lo, Jia Zhu, Scott G. Hansen, Timothy Carroll, Christina Farr Zuend, Laura Nöel-Romas, Zhong-Min Ma, Linda Fritts, Meei-Li Huang, Sijie Sun, Ying Huang, David M. Koelle, Louis J. Picker, Adam Burgener, Lawrence Corey, Christopher J. Miller
  • Absence of β6 Integrin Reduces Influenza Disease Severity in Highly Susceptible Obese Mice
    Pathogenesis and Immunity | Spotlight
    Absence of β6 Integrin Reduces Influenza Disease Severity in Highly Susceptible Obese Mice

    Obesity is a risk factor for developing severe influenza virus infection. However, the reasons for this are unknown. We found that the lungs of obese mice have increased expression of the epithelial integrin β6, a host factor associated with increased disease severity. Knocking out integrin β6 in obese mice favorably altered the pulmonary environment by increasing type I IFN signaling, resulting in decreased viral spread, reduced lung...

    Victoria Meliopoulos, Brandi Livingston, Lee-Ann Van de Velde, Rebekah Honce, Stacey Schultz-Cherry
  • Deletion of both the Tyrosine-Based Endocytosis Signal and the Endoplasmic Reticulum Retrieval Signal in the Cytoplasmic Tail of Spike Protein Attenuates Porcine Epidemic Diarrhea Virus in Pigs
    Pathogenesis and Immunity
    Deletion of both the Tyrosine-Based Endocytosis Signal and the Endoplasmic Reticulum Retrieval Signal in the Cytoplasmic Tail of Spike Protein Attenuates Porcine Epidemic Diarrhea Virus in Pigs

    Many coronaviruses (CoVs) possess conserved motifs YxxΦ and/or KxHxx/KKxx in the cytoplasmic tail of the S protein. The KxHxx/KKxx motif has been identified as the ER retrieval signal, but the function of the YxxΦ motif in the intracellular sorting of CoV S proteins remains controversial. In this study, we showed that the YxxΦ of PEDV S protein is an endocytosis signal. Furthermore, using reverse genetics technology, we evaluated its...

    Yixuan Hou, Tea Meulia, Xiang Gao, Linda J. Saif, Qiuhong Wang
  • Open Access
    Human Norovirus Epitope D Plasticity Allows Escape from Antibody Immunity without Loss of Capacity for Binding Cellular Ligands
    Pathogenesis and Immunity
    Human Norovirus Epitope D Plasticity Allows Escape from Antibody Immunity without Loss of Capacity for Binding Cellular Ligands

    Human norovirus causes ∼20% of all acute gastroenteritis and ∼200,000 deaths per year, primarily in young children. Most epidemic and all pandemic waves of disease over the past 30 years have been caused by type GII.4 human norovirus strains. The capsid sequence of GII.4 strains is changing over time, resulting in viruses with altered ligand and antibody binding characteristics. The carbohydrate binding pocket of these strains does not...

    Lisa C. Lindesmith, Paul D. Brewer-Jensen, Michael L. Mallory, Boyd Yount, Matthew H. Collins, Kari Debbink, Rachel L. Graham, Ralph S. Baric

Author Correction

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    Correction for Gladue et al., “Foot-and-Mouth Disease Virus Modulates Cellular Vimentin for Virus Survival”
    Author Correction
    Correction for Gladue et al., “Foot-and-Mouth Disease Virus Modulates Cellular Vimentin for Virus Survival”
    D. P. Gladue, V. O’Donnell, R. Baker-Branstetter, L. G. Holinka, J. M. Pacheco, I. Fernández Sainz, Z. Lu, X. Ambroggio, L. Rodriguez, M. V. Borca

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Journal of Virology: 93 (2)

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volume 93, issue 2
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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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