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Table of Contents

January 2019; Volume 93,Issue 1

Spotlight

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

Gem

  • Free
    Going the Distance: Optimizing RNA-Seq Strategies for Transcriptomic Analysis of Complex Viral Genomes
    Gem
    Going the Distance: Optimizing RNA-Seq Strategies for Transcriptomic Analysis of Complex Viral Genomes

    Transcriptome profiling has become routine in studies of many biological processes. However, the favored approaches such as short-read Illumina RNA sequencing are giving way to long-read sequencing platforms better suited to interrogating the complex transcriptomes typical of many RNA and DNA viruses.

    Daniel P. Depledge, Ian Mohr, Angus C. Wilson

Structure and Assembly

  • Open Access
    Structure-Based Classification Defines the Discrete Conformational Classes Adopted by the Arenaviral GP1
    Structure and Assembly
    Structure-Based Classification Defines the Discrete Conformational Classes Adopted by the Arenaviral GP1

    The genetically and geographically diverse group of viruses within the family Arenaviridae includes a number of zoonotic pathogens capable of causing fatal hemorrhagic fever. The multisubunit GPC glycoprotein spike complex displayed on the arenavirus envelope is a key determinant of species tropism and a primary target of the host humoral immune response. Here, we show that the receptor-binding GP1 subcomponent of the GPC spike...

    Rhys Pryce, Weng M. Ng, Antra Zeltina, Yasunori Watanabe, Kamel El Omari, Armin Wagner, Thomas A. Bowden
  • Defining HIV-1 Envelope N-Glycan Microdomains through Site-Specific Heterogeneity Profiles
    Structure and Assembly
    Defining HIV-1 Envelope N-Glycan Microdomains through Site-Specific Heterogeneity Profiles

    The Env protein of HIV is highly glycosylated, and the sites of glycosylation can change as the virus mutates during immune evasion. Due to these changes, the glycan location and heterogeneity of surrounding N-glycosylation sites can be altered, resulting in exposure of different glycan or proteoglycan surfaces while still producing a viable HIV variant. These changes present a need for vaccine developers to identify Env variants with...

    Audra A. Hargett, Qing Wei, Barbora Knoppova, Stacy Hall, Zhi-Qiang Huang, Amol Prakash, Todd J. Green, Zina Moldoveanu, Milan Raska, Jan Novak, Matthew B. Renfrow
  • High-Resolution Structural Characterization of a New Adeno-associated Virus Serotype 5 Antibody Epitope toward Engineering Antibody-Resistant Recombinant Gene Delivery Vectors
    Structure and Assembly
    High-Resolution Structural Characterization of a New Adeno-associated Virus Serotype 5 Antibody Epitope toward Engineering Antibody-Resistant Recombinant Gene Delivery Vectors

    Biologics based on recombinant AAVs (rAAVs) are increasingly becoming attractive human gene delivery vehicles, especially after the approval of Glybera in Europe and Luxturna in the United States. However, preexisting neutralizing antibodies against the AAV capsids in a large percentage of the human population limit wide-spread utilization of these vectors. To circumvent this problem, stealth vectors must be generated that are...

    Ariana Jose, Mario Mietzsch, J. Kennon Smith, Justin Kurian, Paul Chipman, Robert McKenna, John Chiorini, Mavis Agbandje-McKenna

Genome Replication and Regulation of Viral Gene Expression

  • The Interaction between ORF18 and ORF30 Is Required for Late Gene Expression in Kaposi's Sarcoma-Associated Herpesvirus
    Genome Replication and Regulation of Viral Gene Expression
    The Interaction between ORF18 and ORF30 Is Required for Late Gene Expression in Kaposi's Sarcoma-Associated Herpesvirus

    Kaposi’s sarcoma-associated herpesvirus (KSHV) is the etiologic agent of Kaposi’s sarcoma and other B-cell cancers and remains a leading cause of death in immunocompromised individuals. A key step in the production of infectious virions is the transcription of viral late genes, which generates capsid and structural proteins and requires the coordination of six viral proteins that form a complex. The role of these proteins during...

    Angelica F. Castañeda, Britt A. Glaunsinger

Genetic Diversity and Evolution

  • Open Access
    Low-Bias RNA Sequencing of the HIV-2 Genome from Blood Plasma
    Genetic Diversity and Evolution
    Low-Bias RNA Sequencing of the HIV-2 Genome from Blood Plasma

    An accurate picture of viral genetic diversity is critical for the development of a globally effective HIV vaccine. However, sequencing strategies are often complicated by target enrichment prior to sequencing, introducing biases that can distort variant frequencies, which are not easily corrected for in downstream analyses. Additionally, detailed a priori sequence knowledge is needed to inform robust primer design when...

    Katherine L. James, Thushan I. de Silva, Katherine Brown, Hilton Whittle, Stephen Taylor, Gilean McVean, Joakim Esbjörnsson, Sarah L. Rowland-Jones
  • A 1,000-Year-Old RNA Virus
    Genetic Diversity and Evolution | Spotlight
    A 1,000-Year-Old RNA Virus

    A virus related to plant chrysoviruses was found in numerous ancient samples of maize, with nearly complete genomes in three samples. The age of the ancient samples (i.e., about 1,000 years old) was confirmed by carbon dating. Chrysoviruses are persistent plant viruses. They infect their hosts from generation to generation by transmission through seeds and can remain in their hosts for very long time periods. When modern corn samples...

    Mahtab Peyambari, Sylvia Warner, Nicholas Stoler, Drew Rainer, Marilyn J. Roossinck
  • Multiple Introductions and Antigenic Mismatch with Vaccines May Contribute to Increased Predominance of G12P[8] Rotaviruses in the United States
    Genetic Diversity and Evolution | Spotlight
    Multiple Introductions and Antigenic Mismatch with Vaccines May Contribute to Increased Predominance of G12P[8] Rotaviruses in the United States

    Rotavirus is an important cause of childhood diarrheal disease worldwide. Two immunodominant proteins of rotavirus, VP7 and VP4, determine G and P genotypes, respectively. Recently, G12P[8] rotaviruses have become increasingly predominant. By analyzing rotavirus genome sequences from stool specimens obtained in Nashville, TN, from 2011 to 2013 and globally circulating rotaviruses, we found evidence of multiple introductions of G12 genes...

    Kristen M. Ogden, Yi Tan, Asmik Akopov, Laura S. Stewart, Rendie McHenry, Christopher J. Fonnesbeck, Bhinnata Piya, Maximilian H. Carter, Nadia B. Fedorova, Rebecca A. Halpin, Meghan H. Shilts, Kathryn M. Edwards, Daniel C. Payne, Mathew D. Esona, Slavica Mijatovic-Rustempasic, James D. Chappell, John T. Patton, Natasha B. Halasa, Suman R. Das
  • Genotypic and Mechanistic Characterization of Subtype-Specific HIV Adaptation to Host Cellular Immunity
    Genetic Diversity and Evolution
    Genotypic and Mechanistic Characterization of Subtype-Specific HIV Adaptation to Host Cellular Immunity

    The identification of HIV polymorphisms reproducibly selected under pressure by specific HLA alleles and the elucidation of their impact on viral function can help identify immunogenic viral regions where immune escape incurs a fitness cost. However, our knowledge of HLA-driven escape pathways and their functional costs is largely limited to HIV subtype B and, to a lesser extent, subtype C. Our study represents the first...

    Natalie N. Kinloch, Guinevere Q. Lee, Jonathan M. Carlson, Steven W. Jin, Chanson J. Brumme, Helen Byakwaga, Conrad Muzoora, Mwebesa B. Bwana, Kyle D. Cobarrubias, Peter W. Hunt, Jeff N. Martin, Mary Carrington, David R. Bangsberg, P. Richard Harrigan, Mark A. Brockman, Zabrina L. Brumme
  • Open Access
    Amino Acid Residue 217 in the Hemagglutinin Glycoprotein Is a Key Mediator of Avian Influenza H7N9 Virus Antigenicity
    Genetic Diversity and Evolution
    Amino Acid Residue 217 in the Hemagglutinin Glycoprotein Is a Key Mediator of Avian Influenza H7N9 Virus Antigenicity

    Avian influenza H7N9 viruses circulating in poultry and wild birds continue to evolve and acquire important phenotypic changes. Mutations to the virus hemagglutinin (HA) glycoprotein can modulate virus antigenicity and facilitate virus escape from natural or vaccine-induced immunity. The focus of this study was to identify evolutionary markers in the HA of H7N9 that drive escape from antibody-based immunity. To achieve this, we...

    Pengxiang Chang, Joshua E. Sealy, Jean-Remy Sadeyen, Munir Iqbal

Virus-Cell Interactions

  • Influenza A Virus Utilizes Low-Affinity, High-Avidity Interactions with the Nuclear Import Machinery To Ensure Infection and Immune Evasion
    Virus-Cell Interactions
    Influenza A Virus Utilizes Low-Affinity, High-Avidity Interactions with the Nuclear Import Machinery To Ensure Infection and Immune Evasion

    We used intracellular nanobodies to block influenza virus infection at the step prior to nuclear import of its ribonucleoproteins. By doing so, we were able to answer an important but outstanding question that could not be addressed with conventional tools: how many of the ∼500 available NLS motifs are needed to establish infection? Furthermore, by controlling the subcellular localization of the incoming viral ribonucleoproteins and...

    Jaime Tome-Amat, Irene Ramos, Ferdinand Amanor, Ana Fernández-Sesma, Joseph Ashour
  • P2X Antagonists Inhibit HIV-1 Productive Infection and Inflammatory Cytokines Interleukin-10 (IL-10) and IL-1β in a Human Tonsil Explant Model
    Virus-Cell Interactions
    P2X Antagonists Inhibit HIV-1 Productive Infection and Inflammatory Cytokines Interleukin-10 (IL-10) and IL-1β in a Human Tonsil Explant Model

    Patients who are chronically infected with HIV-1 experience sequelae related to chronic inflammation. The mechanisms of this inflammation have not been elucidated. Here, we describe a class of drugs that target the P2X proinflammatory signaling receptors in a human tonsil explant model. This model highlights differences in HIV-1 stimulation of lymphoid tissue inflammation and peripheral blood. These drugs serve to block both HIV-1...

    Alexandra Y. Soare, Natasha D. Durham, Ramya Gopal, Benjamin Tweel, Kevin W. Hoffman, Julia A. Brown, Megan O’Brien, Nina Bhardwaj, Jean K. Lim, Benjamin K. Chen, Talia H. Swartz
  • Human MxB Inhibits the Replication of Hepatitis C Virus
    Virus-Cell Interactions
    Human MxB Inhibits the Replication of Hepatitis C Virus

    Viruses of the Flaviviridae family cause major illness and death around the world and thus pose a great threat to human health. Here we show that IFN-inducible MxB restricts several members of the Flaviviridae, including HCV, Japanese encephalitis virus, and dengue virus. This finding not only suggests an active role of MxB in combating these major pathogenic human viruses but also significantly expands the antiviral...

    Dong-Rong Yi, Ni An, Zhen-Long Liu, Feng-Wen Xu, Kavita Raniga, Quan-Jie Li, Rui Zhou, Jing Wang, Yong-Xin Zhang, Jin-Ming Zhou, Lei-Liang Zhang, Jing An, Cheng-Feng Qin, Fei Guo, Xiao-Yu Li, Chen Liang, Shan Cen
  • Identification of Antinorovirus Genes in Human Cells Using Genome-Wide CRISPR Activation Screening
    Virus-Cell Interactions
    Identification of Antinorovirus Genes in Human Cells Using Genome-Wide CRISPR Activation Screening

    Norovirus is one of the leading causes of food-borne illness worldwide. Despite its prevalence, our understanding of norovirus biology is limited due to the difficulty in growing human norovirus in vitro and a lack of an animal model. Murine norovirus (MNoV) is a model norovirus system because MNoV replicates robustly in cell culture and in mice. To identify host genes that can restrict norovirus replication when overexpressed...

    Robert C. Orchard, Meagan E. Sullender, Bria F. Dunlap, Dale R. Balce, John G. Doench, Herbert W. Virgin
  • Contribution of DNA Replication to the FAM111A-Mediated Simian Virus 40 Host Range Phenotype
    Virus-Cell Interactions | Spotlight
    Contribution of DNA Replication to the FAM111A-Mediated Simian Virus 40 Host Range Phenotype

    SV40 has served as a powerful tool for understanding fundamental viral and cellular processes; however, despite extensive study, the SV40 HR mutant phenotype remains poorly understood. Mutations in the C terminus of large T antigen that disrupt binding to the host protein FAM111A render SV40 HR viruses unable to replicate in restrictive cell types. Our work reveals a defect of HR mutant viruses in the formation of viral replication...

    Roxana M. Tarnita, Adrian R. Wilkie, James A. DeCaprio
  • The 11-Kilodalton Nonstructural Protein of Human Parvovirus B19 Facilitates Viral DNA Replication by Interacting with Grb2 through Its Proline-Rich Motifs
    Virus-Cell Interactions | Spotlight
    The 11-Kilodalton Nonstructural Protein of Human Parvovirus B19 Facilitates Viral DNA Replication by Interacting with Grb2 through Its Proline-Rich Motifs

    Human parvovirus B19 (B19V) infection causes hematological disorders and is the leading cause of nonimmunological fetal hydrops during pregnancy. During infection, B19V expresses two structural proteins, VP1 and VP2, and three nonstructural proteins, NS1, 11-kDa, and 7.5-kDa. While NS1 is essential, 11-kDa plays an enhancing role in viral DNA replication. Here, we elucidated a mechanism underlying 11-kDa protein-regulated B19V DNA...

    Peng Xu, Aaron Yun Chen, Safder S. Ganaie, Fang Cheng, Weiran Shen, Xiaomei Wang, Steve Kleiboeker, Yi Li, Jianming Qiu
  • αvβ3 Integrin Is Required for Efficient Infection of Epithelial Cells with Human Adenovirus Type 26
    Virus-Cell Interactions
    αvβ3 Integrin Is Required for Efficient Infection of Epithelial Cells with Human Adenovirus Type 26

    Adenovirus-based vectors are used today for gene transfer and vaccination. HAdV26 has emerged as a promising candidate vector for development of vaccines due to its relatively low seroprevalence and its ability to induce potent immune responses against inserted transgenes. However, data regarding the basic biology of the virus, like receptor usage or intracellular trafficking, are limited. In this work, we found that efficient infection...

    Davor Nestić, Taco G. Uil, Jiangtao Ma, Soumitra Roy, Jort Vellinga, Andrew H. Baker, Jerome Custers, Dragomira Majhen
  • Synergistic Activation of Bovine Herpesvirus 1 Productive Infection and Viral Regulatory Promoters by the Progesterone Receptor and Krüppel-Like Transcription Factor 15
    Virus-Cell Interactions
    Synergistic Activation of Bovine Herpesvirus 1 Productive Infection and Viral Regulatory Promoters by the Progesterone Receptor and Krüppel-Like Transcription Factor 15

    Bovine herpesvirus 1 (BoHV-1) is the most frequently diagnosed cause of abortions in pregnant cows and can cause “abortion storms” in susceptible herds. Virulent field strains and even commercially available modified live vaccines can induce abortion, in part because BoHV-1 replicates efficiently in the ovary and corpus luteum. We now demonstrate that progesterone and the progesterone receptor (PR) stimulate productive infection. The...

    Fouad S. El-mayet, Ayman S. El-Habbaa, Jean D’Offay, Clinton Jones
  • The C Terminus of Rotavirus VP4 Protein Contains an Actin Binding Domain Which Requires Cooperation with the Coiled-Coil Domain for Actin Remodeling
    Virus-Cell Interactions
    The C Terminus of Rotavirus VP4 Protein Contains an Actin Binding Domain Which Requires Cooperation with the Coiled-Coil Domain for Actin Remodeling

    Rotaviruses are causal agents of acute infantile viral diarrhea. In intestinal cells, in vitro as well as in vivo, virus assembly and exit do not imply cell lysis but rely on an active process in which the cytoskeleton plays a major role. We describe here a novel molecular mechanism by which the rotavirus spike protein VP4 drives actin remodeling. This relies on the fact that VP4 occurs in different forms. Besides its...

    Wilfried Condemine, Thibaut Eguether, Nathalie Couroussé, Catherine Etchebest, Agnes Gardet, Germain Trugnan, Serge Chwetzoff
  • Structural Adaptations of Norovirus GII.17/13/21 Lineage through Two Distinct Evolutionary Paths
    Virus-Cell Interactions
    Structural Adaptations of Norovirus GII.17/13/21 Lineage through Two Distinct Evolutionary Paths

    Our understanding of the molecular bases behind the interplays between human noroviruses and their host glycan ligands, as well as their evolutionary changes over time with alterations in their host ligand binding capability and host susceptibility, remains limited. By solving the crystal structures of the glycan ligand binding protruding (P) domains with or without glycan ligands of three representative noroviruses of the GII.17/13/21...

    Ying Qian, Mohan Song, Xi Jiang, Ming Xia, Jarek Meller, Ming Tan, Yutao Chen, Xuemei Li, Zihe Rao

Cellular Response to Infection

  • Broad Recognition of Circulating HIV-1 by HIV-1-Specific Cytotoxic T-Lymphocytes with Strong Ability to Suppress HIV-1 Replication
    Cellular Response to Infection
    Broad Recognition of Circulating HIV-1 by HIV-1-Specific Cytotoxic T-Lymphocytes with Strong Ability to Suppress HIV-1 Replication

    In recent T-cell AIDS vaccine trials, the vaccines did not prevent HIV-1 infection, although HIV-1-specific T cells were induced in the vaccinated individuals, suggesting that the T cells have a weak ability to suppress HIV-1 replication and fail to recognize circulating HIV-1. We previously demonstrated that the T-cell responses to 10 epitopes were significantly associated with good clinical outcome. However, there is no direct...

    Hayato Murakoshi, Nozomi Kuse, Tomohiro Akahoshi, Yu Zhang, Takayuki Chikata, Mohamed Ali Borghan, Hiroyuki Gatanaga, Shinichi Oka, Keiko Sakai, Masafumi Takiguchi

Vaccines and Antiviral Agents

  • Engineered Small-Molecule Control of Influenza A Virus Replication
    Vaccines and Antiviral Agents
    Engineered Small-Molecule Control of Influenza A Virus Replication

    Influenza A virus (IAV) causes significant morbidity and mortality annually worldwide, despite the availability of new formulations of the vaccine each season. There is a critical need to develop more-efficacious vaccines. However, testing novel vaccines in the human population in controlled studies is difficult due to the limited availability and efficacy of intervention strategies should the vaccine fail. There are also significant...

    Elizabeth J. Fay, Stephanie L. Aron, Ian A. Stone, Barbara M. Waring, Richard K. Plemper, Ryan A. Langlois

Pathogenesis and Immunity

  • Open Access
    Naturally Occurring Single Mutations in Ebola Virus Observably Impact Infectivity
    Pathogenesis and Immunity
    Naturally Occurring Single Mutations in Ebola Virus Observably Impact Infectivity

    During the Ebola virus (EBOV) disease outbreak in West Africa in 2014–2016, it was discovered that several mutations in the virus emerged and became prevalent in the human population. This suggests that these mutations may play a role impacting viral fitness. We investigated three of these previously identified mutations (in the glycoprotein [GP], nucleoprotein [NP], or RNA-dependent RNA polymerase [L]) in cell culture, as well as in...

    Gary Wong, Shihua He, Anders Leung, Wenguang Cao, Yuhai Bi, Zirui Zhang, Wenjun Zhu, Liang Wang, Yuhui Zhao, Keding Cheng, Di Liu, Wenjun Liu, Darwyn Kobasa, George F. Gao, Xiangguo Qiu
  • Bone Marrow-Derived CD4<sup>+</sup> T Cells Are Depleted in Simian Immunodeficiency Virus-Infected Macaques and Contribute to the Size of the Replication-Competent Reservoir
    Pathogenesis and Immunity
    Bone Marrow-Derived CD4+ T Cells Are Depleted in Simian Immunodeficiency Virus-Infected Macaques and Contribute to the Size of the Replication-Competent Reservoir

    The latent viral reservoir is one of the major obstacles in purging the immune system of HIV. It is paramount that we elucidate which anatomic compartments harbor replication-competent virus, which upon ART interruption results in viral rebound and pathogenesis. In this study, using the rhesus macaque model of SIV infection and ART, we examined the immunologic status of the BM and its role as a potential sanctuary for latent virus. We...

    Timothy N. Hoang, Justin L. Harper, Maria Pino, Hong Wang, Luca Micci, Colin T. King, Colleen S. McGary, Julia B. McBrien, Barbara Cervasi, Guido Silvestri, Mirko Paiardini
  • Risk Assessment of Fifth-Wave H7N9 Influenza A Viruses in Mammalian Models
    Pathogenesis and Immunity | Spotlight
    Risk Assessment of Fifth-Wave H7N9 Influenza A Viruses in Mammalian Models

    The potential pandemic risk posed by avian influenza H7N9 viruses was heightened during the fifth epidemic wave in China due to the sudden increase in the number of human infections and the emergence of antigenically distinct LPAI and HPAI H7N9 viruses. In this study, a group of fifth-wave HPAI and LPAI viruses was evaluated for its ability to infect, cause disease, and transmit in small-animal models. The ability of HPAI H7N9 viruses...

    Xiangjie Sun, Jessica A. Belser, Claudia Pappas, Joanna A. Pulit-Penaloza, Nicole Brock, Hui Zeng, Hannah M. Creager, Shoshona Le, Malania Wilson, Amanda Lewis, Thomas J. Stark, Wun-Ju Shieh, John Barnes, Terrence M. Tumpey, Taronna R. Maines

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Journal of Virology: 93 (1)

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volume 93, issue 1
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  • Receptor Recognition by the Novel Coronavirus from Wuhan: an Analysis Based on Decade-Long Structural Studies of SARS Coronavirus
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