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Table of Contents

August 2020; Volume 94,Issue 16

Spotlight

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

Genome Replication and Regulation of Viral Gene Expression

  • Porcine Epidemic Diarrhea Virus Deficient in RNA Cap Guanine-N-7 Methylation Is Attenuated and Induces Higher Type I and III Interferon Responses
    Genome Replication and Regulation of Viral Gene Expression | Spotlight
    Porcine Epidemic Diarrhea Virus Deficient in RNA Cap Guanine-N-7 Methylation Is Attenuated and Induces Higher Type I and III Interferon Responses

    Coronaviruses (CoVs) include a wide range of important human and animal pathogens. Examples of human CoVs include severe acute respiratory syndrome coronavirus (SARS-CoV-1), Middle East respiratory syndrome coronavirus (MERS-CoV), and the most recently emerged SARS-CoV-2. Examples of pig CoVs include porcine epidemic diarrhea virus (PEDV), porcine deltacoronavirus (PDCoV), and swine enteric alphacoronavirus (SeACoV). There are no...

    Yunjian Lu, Hui Cai, Mijia Lu, Yuanmei Ma, Anzhong Li, Youling Gao, Jiyong Zhou, Howard Gu, Jianrong Li, Jinyan Gu
  • An Extended Primer Grip of Picornavirus Polymerase Facilitates Sexual RNA Replication Mechanisms
    Genome Replication and Regulation of Viral Gene Expression
    An Extended Primer Grip of Picornavirus Polymerase Facilitates Sexual RNA Replication Mechanisms

    Picornaviruses have both asexual and sexual RNA replication mechanisms. Sexual RNA replication shapes picornavirus species groups, contributes to the emergence of vaccine-derived polioviruses, and counteracts error catastrophe. Can viruses distinguish between homologous and nonhomologous partners during sexual RNA replication? We implicate an extended primer grip of the viral polymerase in sexual RNA replication mechanisms. By sensing...

    Brian J. Kempf, Colleen L. Watkins, Olve B. Peersen, David J. Barton
  • <em>cis</em>-Acting Sequences and Secondary Structures in Untranslated Regions of Duck Tembusu Virus RNA Are Important for Cap-Independent Translation and Viral Proliferation
    Genome Replication and Regulation of Viral Gene Expression
    cis-Acting Sequences and Secondary Structures in Untranslated Regions of Duck Tembusu Virus RNA Are Important for Cap-Independent Translation and Viral Proliferation

    The genus Flavivirus includes major human pathogens, as well as animal-infecting viruses with zoonotic potential. In order to counteract the threats these viruses represent, it is important to understand their basic biology to develop universal attenuation strategies. Here, we demonstrate that five different flaviviruses use cap-independent translation, indicating that the phenomenon is probably common to all members of the...

    Tao Wang, Andres Merits, Yuanyuan Wu, Mingshu Wang, Renyong Jia, Dekang Zhu, Mafeng Liu, Xinxin Zhao, Qiao Yang, Ying Wu, Shaqiu Zhang, Yunya Liu, Ling Zhang, Yanling Yu, Leichang Pan, Shun Chen, Anchun Cheng
  • Ebola Virus Inclusion Body Formation and RNA Synthesis Are Controlled by a Novel Domain of Nucleoprotein Interacting with VP35
    Genome Replication and Regulation of Viral Gene Expression
    Ebola Virus Inclusion Body Formation and RNA Synthesis Are Controlled by a Novel Domain of Nucleoprotein Interacting with VP35

    Inclusion bodies (IBs) are cytoplasmic sites of RNA synthesis for a variety of negative-sense RNA viruses, including Ebola virus. In addition to housing important steps in the viral life cycle, IBs protect new viral RNA from innate immune attack and contain specific host proteins whose function is under study. A key viral factor in Ebola virus IB formation is the nucleoprotein, NP, which also is important in RNA encapsidation and...

    Tsuyoshi Miyake, Charlotte M. Farley, Benjamin E. Neubauer, Thomas P. Beddow, Thomas Hoenen, Daniel A. Engel

Genetic Diversity and Evolution

  • Host-Virus Arms Races Drive Elevated Adaptive Evolution in Viral Receptors
    Genetic Diversity and Evolution | Spotlight
    Host-Virus Arms Races Drive Elevated Adaptive Evolution in Viral Receptors

    Viruses hijack cellular proteins, termed viral receptors, to assist their entry into host cells. While viral receptors experience negative selection to maintain their normal functions, they also undergo positive selection due to an everlasting evolutionary arms race between viruses and hosts. A complete picture on how viral receptors evolve under two conflicting forces is still lacking. In this study, we systematically analyzed the...

    Wenqiang Wang, Huayao Zhao, Guan-Zhu Han

Virus-Cell Interactions

  • Human Cytomegalovirus Glycoprotein-Initiated Signaling Mediates the Aberrant Activation of Akt
    Virus-Cell Interactions
    Human Cytomegalovirus Glycoprotein-Initiated Signaling Mediates the Aberrant Activation of Akt

    Human cytomegalovirus (HCMV) infection is endemic throughout the world regardless of socioeconomic conditions and geographic locations with a seroprevalence reaching up to 100% in some developing countries. Although asymptomatic in healthy individuals, HCMV can cause severe multiorgan disease in immunocompromised or immunonaive patients. HCMV disease is a direct consequence of monocyte-mediated systematic spread of the virus following...

    Jamil Mahmud, Michael J. Miller, Aaron M. Altman, Gary C. Chan
  • Cellular Vimentin Interacts with Foot-and-Mouth Disease Virus Nonstructural Protein 3A and Negatively Modulates Viral Replication
    Virus-Cell Interactions
    Cellular Vimentin Interacts with Foot-and-Mouth Disease Virus Nonstructural Protein 3A and Negatively Modulates Viral Replication

    Foot-and-mouth disease virus (FMDV) nonstructural protein 3A plays important roles in virus replication, host range, and virulence. To further understand the role of 3A during FMDV infection, identification of host cell factors that interact with FMDV 3A is needed. Here, we found that vimentin is a direct binding partner of FMDV 3A, and manipulation of vimentin has a negative effect on virus replication. We also demonstrated that amino...

    Xueqing Ma, Ying Ling, Pinghua Li, Pu Sun, Yimei Cao, Xingwen Bai, Kun Li, Yuanfang Fu, Jing Zhang, Dong Li, Huifang Bao, Yingli Chen, Zhiyong Li, Yonggang Wang, Zengjun Lu, Zaixin Liu
  • Differential Pressures of SERINC5 and IFITM3 on HIV-1 Envelope Glycoprotein over the Course of HIV-1 Infection
    Virus-Cell Interactions
    Differential Pressures of SERINC5 and IFITM3 on HIV-1 Envelope Glycoprotein over the Course of HIV-1 Infection

    HIV-1 Env protein is exposed to the inhibition not only by humoral response, but also by host restriction factors, including serine incorporator 5 (SERINC5) and interferon-inducible transmembrane 3 (IFITM3). This study investigates how HIV-1 envelope glycoprotein (Env) manages to overcome the pressures from all these different host inhibition mechanisms over the long course of viral infection. HIV-1 Env preserves the resistance to...

    Saina Beitari, Qinghua Pan, Andrés Finzi, Chen Liang
  • Human Papillomavirus 31 Tyrosine 102 Regulates Interaction with E2 Binding Partners and Episomal Maintenance
    Virus-Cell Interactions
    Human Papillomavirus 31 Tyrosine 102 Regulates Interaction with E2 Binding Partners and Episomal Maintenance

    Posttranslational modifications by phosphorylation can change protein activities, binding partners, or localization. Tyrosine 102 is conserved between delta papillomavirus BPV-1 and alpha papillomavirus HPV-31 E2. We characterized mutations of HPV-31 E2 for interactions with relevant cellular binding partners and replication in the context of the viral genome.

    Timra Gilson, Sara Culleton, Fang Xie, Marsha DeSmet, Elliot J. Androphy
  • Human Cytomegalovirus Utilizes Extracellular Vesicles To Enhance Virus Spread
    Virus-Cell Interactions
    Human Cytomegalovirus Utilizes Extracellular Vesicles To Enhance Virus Spread

    Human cytomegalovirus (HCMV) is a herpesvirus that leads to serious health consequences in neonatal or immunocompromised patients. Clinical management of infection in these at-risk groups remains a serious concern even with approved antiviral therapies available. It is necessary to increase our understanding of the cellular changes that occur during infection and their importance to virus spread. This may help to identify new targets...

    Nicholas T. Streck, Yuanjun Zhao, Jeffrey M. Sundstrom, Nicholas J. Buchkovich
  • Open Access
    Exocytosis of Progeny Infectious Varicella-Zoster Virus Particles via a Mannose-6-Phosphate Receptor Pathway without Xenophagy following Secondary Envelopment
    Virus-Cell Interactions
    Exocytosis of Progeny Infectious Varicella-Zoster Virus Particles via a Mannose-6-Phosphate Receptor Pathway without Xenophagy following Secondary Envelopment

    The long-term goal of this research has been to determine why VZV, when grown in cultured cells, invariably is more cell associated and has a lower titer than other alphaherpesviruses, such as herpes simplex virus 1 (HSV1) or pseudorabies virus (PRV). Data from both HSV1 and PRV laboratories have identified a Rab6 secretory pathway for the transport of single enveloped viral particles from the trans-Golgi network within small...

    James H. Girsch, Wallen Jackson, John E. Carpenter, Thomas O. Moninger, Keith W. Jarosinski, Charles Grose
  • ORF4 of the Temperate Archaeal Virus SNJ1 Governs the Lysis-Lysogeny Switch and Superinfection Immunity
    Virus-Cell Interactions
    ORF4 of the Temperate Archaeal Virus SNJ1 Governs the Lysis-Lysogeny Switch and Superinfection Immunity

    Archaeal viruses are important parts of the virosphere. Understanding how they regulate their life cycles and interact with host cells provide crucial insights into their biological functions and the evolutionary histories of viruses. However, mechanistic studies of the life cycle of archaeal viruses are scarce due to a lack of genetic tools and demanding cultivation conditions. Here, we discover that the temperate haloarchaeal virus...

    Beibei Chen, Zhao Chen, Yuchen Wang, Han Gong, Linshan Sima, Jiao Wang, Shushan Ouyang, Wenqiang Gan, Mart Krupovic, Xiangdong Chen, Shishen Du
  • An Alternatively Spliced Sirtuin 2 Isoform 5 Inhibits Hepatitis B Virus Replication from cccDNA by Repressing Epigenetic Modifications Made by Histone Lysine Methyltransferases
    Virus-Cell Interactions
    An Alternatively Spliced Sirtuin 2 Isoform 5 Inhibits Hepatitis B Virus Replication from cccDNA by Repressing Epigenetic Modifications Made by Histone Lysine Methyltransferases

    Sirt2, a predominant cytoplasmic α-tubulin deacetylase, promotes the growth of hepatocellular carcinoma; indeed, HBV replication increases Sirt2 expression, and overexpression of Sirt2 is associated with hepatic fibrosis and epithelial-to-mesenchymal transition. Increased amounts of Sirt2 isoforms 1, 2, and 5 upon HBV replication might further upregulate HBV replication, leading to a vicious cycle of virus replication/disease...

    Zahra Zahid Piracha, Umar Saeed, Jumi Kim, Hyeonjoong Kwon, Yong-Joon Chwae, Hyun Woong Lee, Jin Hong Lim, Sun Park, Ho-Joon Shin, Kyongmin Kim
  • Open Access
    Patterns of Herpes Simplex Virus 1 Infection in Neural Progenitor Cells
    Virus-Cell Interactions
    Patterns of Herpes Simplex Virus 1 Infection in Neural Progenitor Cells

    This study employed human induced pluripotent stem cells (hiPSCs) to model the interaction of HSV-1 with NPCs, which reside in the neurogenic niches of the CNS and play a fundamental role in adult neurogenesis. Herein, we provide evidence that in NPCs infected at an MOI as low as 0.001, HSV-1 can establish a latent state, suggesting that (i) a variant of classical HSV-1 latency can be established during earlier stages of neuronal...

    Wenxiao Zheng, Alissa M. Klammer, Jennifer N. Naciri, Jason Yeung, Matthew Demers, Jadranka Milosevic, Paul R. Kinchington, David C. Bloom, Vishwajit L. Nimgaonkar, Leonardo D’Aiuto
  • Open Access
    Filoviruses Use the HOPS Complex and UVRAG To Traffic to Niemann-Pick C1 Compartments during Viral Entry
    Virus-Cell Interactions | Spotlight
    Filoviruses Use the HOPS Complex and UVRAG To Traffic to Niemann-Pick C1 Compartments during Viral Entry

    Ebola viruses (EBOV) and other filoviruses cause sporadic and unpredictable outbreaks of highly lethal diseases. The lack of FDA-approved therapeutics, particularly ones with panfiloviral specificity, highlights the need for continued research efforts to understand aspects of the viral life cycle that are common to all filoviruses. As such, viral entry is of particular interest, as all filoviruses must reach cellular compartments...

    Yuxia Bo, Shirley Qiu, Rory P. Mulloy, Marceline Côté

Cellular Response to Infection

  • Butyrate Reprograms Expression of Specific Interferon-Stimulated Genes
    Cellular Response to Infection
    Butyrate Reprograms Expression of Specific Interferon-Stimulated Genes

    Butyrate is a lipid produced by intestinal bacteria. Here, we newly show that butyrate reprograms the innate antiviral immune response mediated by type I interferons (IFNs). Many of the antiviral genes induced by type I IFNs are repressed in the presence of butyrate, resulting in increased virus infection and replication. Our research demonstrates that metabolites produced by the gut microbiome, such as butyrate, can have complex...

    Mahesh Chemudupati, Adam D. Kenney, Anna C. Smith, Robert J. Fillinger, Lizhi Zhang, Ashley Zani, Shan-Lu Liu, Matthew Z. Anderson, Amit Sharma, Jacob S. Yount

Vaccines and Antiviral Agents

  • Enhancing Neuraminidase Immunogenicity of Influenza A Viruses by Rewiring RNA Packaging Signals
    Vaccines and Antiviral Agents
    Enhancing Neuraminidase Immunogenicity of Influenza A Viruses by Rewiring RNA Packaging Signals

    Influenza virus infections are a major source of morbidity and mortality worldwide. Increasing evidence highlights neuraminidase as a potential vaccination target. This report demonstrates the efficacy of rewiring influenza virus packaging signals for creating vaccines with more neuraminidase content which provide better neuraminidase (NA)-based protection.

    Allen Zheng, Weina Sun, Xiaoli Xiong, Alec W. Freyn, Julia Peukes, Shirin Strohmeier, Raffael Nachbagauer, John A. G. Briggs, Florian Krammer, Peter Palese
  • A Temperature-Dependent Translation Defect Caused by Internal Ribosome Entry Site Mutation Attenuates Foot-and-Mouth Disease Virus: Implications for Rational Vaccine Design
    Vaccines and Antiviral Agents
    A Temperature-Dependent Translation Defect Caused by Internal Ribosome Entry Site Mutation Attenuates Foot-and-Mouth Disease Virus: Implications for Rational Vaccine Design

    The World Organization for Animal Health has called for global control and eradication of foot-and-mouth disease (FMD), the most economically and socially devastating disease affecting animal husbandry worldwide. Live-attenuated vaccines are considered the most effective strategy for prevention, control, and eradication of infectious diseases due to their capacity to induce potent and long-lasting protective immunity. However, efforts...

    Decheng Yang, Chao Sun, Rongyuan Gao, Haiwei Wang, Wenming Liu, Kewei Yu, Guohui Zhou, Bo Zhao, Li Yu

Pathogenesis and Immunity

  • Seminal Plasma-Derived Extracellular-Vesicle Fractions from HIV-Infected Men Exhibit Unique MicroRNA Signatures and Induce a Proinflammatory Response in Cells Isolated from the Female Reproductive Tract
    Pathogenesis and Immunity
    Seminal Plasma-Derived Extracellular-Vesicle Fractions from HIV-Infected Men Exhibit Unique MicroRNA Signatures and Induce a Proinflammatory Response in Cells Isolated from the Female Reproductive Tract

    Seminal plasma (SP), the major vehicle for HIV, can modulate HIV transmission risk through a variety of mechanisms. Extracellular vesicles (EVs) are extremely abundant in semen, and because they play a key role in intercellular communication pathways and immune regulation, they may impact the likelihood of HIV transmission. However, little is known about the properties and signaling effects of SP-derived EVs in the context of HIV...

    Erika G. Marques de Menezes, Karen Jang, Ashley F. George, Mette Nyegaard, Jason Neidleman, Heather C. Inglis, Ali Danesh, Xutao Deng, Amirali Afshari, Young H. Kim, Jean-Noël Billaud, Kara Marson, Christopher D. Pilcher, Satish K. Pillai, Philip J. Norris, Nadia R. Roan
  • Restoring Herpesvirus Entry Mediator (HVEM) Immune Function in HVEM<sup>−/−</sup> Mice Rescues Herpes Simplex Virus 1 Latency and Reactivation Independently of Binding to Glycoprotein D
    Pathogenesis and Immunity
    Restoring Herpesvirus Entry Mediator (HVEM) Immune Function in HVEM−/− Mice Rescues Herpes Simplex Virus 1 Latency and Reactivation Independently of Binding to Glycoprotein D

    HSV-1 is a common cause of ocular infections worldwide and a significant cause of preventable blindness. Corneal scarring and blindness are consequences of the immune response induced by repeated reactivation events. Therefore, HSV-1 therapeutic approaches should focus on preventing latency and reactivation. Our data suggest that the immune function of HVEM plays an important role in the HSV-1 latency and reactivation cycle that is...

    Kati Tormanen, Shaohui Wang, Ujjaldeep Jaggi, Homayon Ghiasi
  • Better Viral Control despite Higher CD4<sup>+</sup> T Cell Activation during Acute HIV-1 Infection in Zambian Women Is Linked to the Sex Hormone Estradiol
    Pathogenesis and Immunity | Spotlight
    Better Viral Control despite Higher CD4+ T Cell Activation during Acute HIV-1 Infection in Zambian Women Is Linked to the Sex Hormone Estradiol

    Previous studies have identified sex-specific differences during chronic HIV-1 infection, but little is known about sex differences in the acute phase, or how disparities in the initial response to the virus may affect disease. We demonstrate that restriction of viral load in women begins during acute infection and is maintained into chronic infection. Despite this, women exhibit more rapid CD4+ T cell loss than men. These...

    Elina El-Badry, Gladys Macharia, Daniel Claiborne, Kelsie Brooks, Darío A. Dilernia, Paul Goepfert, William Kilembe, Susan Allen, Jill Gilmour, Eric Hunter
  • Open Access
    Aerosol Transmission from Infected Swine to Ferrets of an H3N2 Virus Collected from an Agricultural Fair and Associated with Human Variant Infections
    Pathogenesis and Immunity | Spotlight
    Aerosol Transmission from Infected Swine to Ferrets of an H3N2 Virus Collected from an Agricultural Fair and Associated with Human Variant Infections

    A recently emerged lineage of human-like H3N2 (H3.2010.1) influenza A virus (IAV) from swine has been frequently detected in commercial and exhibition swine in recent years and has been associated with H3N2 variant cases in humans from 2016 and 2017. To demonstrate a model for characterizing the potential for zoonotic transmission associated with swine IAV, we performed an in vivo study of transmission between pigs infected...

    Bryan S. Kaplan, J. Brian Kimble, Jennifer Chang, Tavis K. Anderson, Phillip C. Gauger, Alicia Janas-Martindale, Mary Lea Killian, Andrew S. Bowman, Amy L. Vincent

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Journal of Virology: 94 (16)

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volume 94, issue 16
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