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Table of Contents

January 2021; Volume 95,Issue 2

Spotlight

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

Minireview

  • Role of Inflammation in Virus Pathogenesis during Pregnancy
    Minireview
    Role of Inflammation in Virus Pathogenesis during Pregnancy

    Viral infections during pregnancy lead to a spectrum of maternal and fetal outcomes, ranging from asymptomatic disease to more critical conditions presenting with severe maternal morbidity, stillbirth, preterm birth, intrauterine growth restriction, and fetal congenital anomalies, either apparent at birth or later in life. In this article, we review the pathogenesis of several viral infections that are particularly relevant in the...

    Anna Chudnovets, Jin Liu, Harish Narasimhan, Yang Liu, Irina Burd

Structure and Assembly

  • Structure of High-Risk Papillomavirus 31 E6 Oncogenic Protein and Characterization of E6/E6AP/p53 Complex Formation
    Structure and Assembly
    Structure of High-Risk Papillomavirus 31 E6 Oncogenic Protein and Characterization of E6/E6AP/p53 Complex Formation

    Variations of carcinogenicity of human papillomaviruses are related to variations of the E6 and E7 interactome. While different HPV species and genera are known to target distinct host proteins, the fine differences between E6 and E7 of closely related HPVs, supposed to target the same cellular protein pools, remain to be addressed. We compare the oncogenic E6 proteins of the closely related high-risk HPV31 and HPV16 with regard to...

    Marcel Chris Conrady, Irina Suarez, Gergö Gogl, Desiree Isabella Frecot, Anna Bonhoure, Camille Kostmann, Alexandra Cousido-Siah, André Mitschler, JiaWen Lim, Murielle Masson, Thomas Iftner, Frank Stubenrauch, Gilles Travé, Claudia Simon

Genome Replication and Regulation of Viral Gene Expression

  • Shared Mechanisms Govern HIV Transcriptional Suppression in Circulating CD103<sup>+</sup> and Gut CD4<sup>+</sup> T Cells
    Genome Replication and Regulation of Viral Gene Expression
    Shared Mechanisms Govern HIV Transcriptional Suppression in Circulating CD103+ and Gut CD4+ T Cells

    The ability of HIV to establish a reversibly silent, “latent” infection is widely regarded as the main barrier to curing HIV. Most HIV-infected cells reside in tissues such as the gut, but it is unclear what mechanisms maintain HIV latency in the blood or gut. We found that circulating CD103+ CD4+ T cells are enriched for HIV-infected cells in a latent-like state. Using RNA sequencing (RNA-seq), we found that CD103...

    Steven A. Yukl, Shahzada Khan, Tsui-Hua Chen, Martin Trapecar, Frank Wu, Guorui Xie, Sushama Telwatte, Daniel Fulop, Alexander R. Pico, Gregory M. Laird, Kristen D. Ritter, Norman G. Jones, Chuanyi M. Lu, Robert F. Siliciano, Nadia R. Roan, Jeffrey M. Milush, Ma Somsouk, Steven G. Deeks, Peter W. Hunt, Shomyseh Sanjabi
  • Control of Archetype BK Polyomavirus MicroRNA Expression
    Genome Replication and Regulation of Viral Gene Expression | Spotlight
    Control of Archetype BK Polyomavirus MicroRNA Expression

    The BK polyomavirus (BKPyV) miRNA plays an important role in regulating viral large-T-antigen expression and limiting the replication of archetype BKPyV, suggesting that the miRNA regulates BKPyV persistence. However, how miRNA expression is regulated is poorly understood. Here, we present evidence that the miRNA is expressed from an intron that is generated by RNA polymerase II transcribing the circular viral genome more than once. We...

    Wei Zou, Gau Shoua Vue, Benedetta Assetta, Heather Manza, Walter J. Atwood, Michael J. Imperiale

Genetic Diversity and Evolution

  • Detection and Characterization of Swine Origin Influenza A(H1N1) Pandemic 2009 Viruses in Humans following Zoonotic Transmission
    Genetic Diversity and Evolution | Spotlight
    Detection and Characterization of Swine Origin Influenza A(H1N1) Pandemic 2009 Viruses in Humans following Zoonotic Transmission

    Influenza virus infects a wide range of hosts, resulting in illnesses that vary from asymptomatic cases to severe pneumonia and death. Viral transfer can occur between human and nonhuman hosts, resulting in human and nonhuman origin viruses circulating in novel hosts. In this work, we have identified the first case of a swine-origin influenza A(H1N1)pdm09 virus resulting in a human infection. This shows that these viruses not only...

    Peter W. Cook, Thomas Stark, Joyce Jones, Rebecca Kondor, Natosha Zanders, Jeffrey Benfer, Samantha Scott, Yunho Jang, Alicia Janas-Martindale, Stephen Lindstrom, Lenee Blanton, John Schiltz, Rachel Tell, Richard Griesser, Peter Shult, Erik Reisdorf, Tonya Danz, Alicia Fry, John Barnes, Amy Vincent, David E. Wentworth, C. Todd Davis
  • A Respiratory Syncytial Virus Attachment Gene Variant Associated with More Severe Disease in Infants Decreases Fusion Protein Expression, Which May Facilitate Immune Evasion
    Genetic Diversity and Evolution | Spotlight
    A Respiratory Syncytial Virus Attachment Gene Variant Associated with More Severe Disease in Infants Decreases Fusion Protein Expression, Which May Facilitate Immune Evasion

    Strain-specific differences in respiratory syncytial virus (RSV) isolates are associated with differential pathogenesis in mice. However, the role of RSV genotypes in human infection is incompletely understood. This work demonstrates that one such genotype, 2stop+A4G, present in the RSV attachment (G) gene terminus is associated with greater infant disease severity. The genotype consists of two tandem stop codons preceding an A-to-G...

    Stacey Human, Anne L. Hotard, Christina A. Rostad, Sujin Lee, Louise McCormick, Emma K. Larkin, Teresa C. T. Peret, Jaume Jorba, Joseph Lanzone, Tebeb Gebretsadik, John V. Williams, Melissa Bloodworth, Matthew Stier, Kecia Carroll, R. Stokes Peebles, Larry J. Anderson, Tina V. Hartert, Martin L. Moore
  • Isolation and Characterization of Porcine Astrovirus 5 from a Classical Swine Fever Virus-Infected Specimen
    Genetic Diversity and Evolution
    Isolation and Characterization of Porcine Astrovirus 5 from a Classical Swine Fever Virus-Infected Specimen

    Porcine astroviruses are mainly associated with gastroenteritis and neurological diseases in pigs, and five genotypes have been identified (PAstV1-5). However, the clinical manifestations of genotypes other than PAstV1 have not yet been determined because of the failure of in vitro virus isolation. Here, we report a surprising isolation of a PAstV5 strain from a clinical classical swine fever virus (CSFV)-infected tissue sample...

    Shijiang Mi, Shibang Guo, Chaonan Xing, Chaoting Xiao, Biao He, Bin Wu, Xianzhu Xia, Changchun Tu, Wenjie Gong
  • Country Level Diversity of the HIV-1 Pandemic between 1990 and 2015
    Genetic Diversity and Evolution
    Country Level Diversity of the HIV-1 Pandemic between 1990 and 2015

    This is the first study to analyze global country level HIV-1 diversity from 1990 to 2015. We found extremely wide variation in complexity of country level HIV diversity around the world. Central African countries have the most diverse HIV epidemics. The number of distinct HIV-1 subtypes and recombinants was greatest in Western Europe and North America. The proportion of HIV-1 infections due to recombinants was highest in South-East...

    Joris Hemelaar, Shanghavie Loganathan, Ramyiadarsini Elangovan, Jason Yun, Leslie Dickson-Tetteh, Shona Kirtley, WHO-UNAIDS Network for HIV Isolation and Characterization

Virus-Cell Interactions

  • Capsid Lattice Destabilization Leads to Premature Loss of the Viral Genome and Integrase Enzyme during HIV-1 Infection
    Virus-Cell Interactions
    Capsid Lattice Destabilization Leads to Premature Loss of the Viral Genome and Integrase Enzyme during HIV-1 Infection

    The human immunodeficiency virus type 1 (HIV-1) capsid (CA) protein forms a conical lattice around the viral RNA genome and the associated viral enzymes and proteins, together constituting the viral core. Upon infection of a new cell, viral cores are released into the cytoplasm where they undergo a process termed “uncoating,” i.e., shedding of CA molecules from the conical lattice. Although proper and timely uncoating has been shown to...

    Jenna E. Eschbach, Jennifer L. Elliott, Wen Li, Kaneil K. Zadrozny, Keanu Davis, Shawn J. Mohammed, Dana Q. Lawson, Owen Pornillos, Alan N. Engelman, Sebla B. Kutluay
  • Eukaryotic Translation Elongation Factor 1 Delta Inhibits the Nuclear Import of the Nucleoprotein and PA-PB1 Heterodimer of Influenza A Virus
    Virus-Cell Interactions
    Eukaryotic Translation Elongation Factor 1 Delta Inhibits the Nuclear Import of the Nucleoprotein and PA-PB1 Heterodimer of Influenza A Virus

    Influenza A virus is the major cause of influenza, a respiratory disease in humans and animals. Different from most other RNA viruses, the transcription and replication of IAV occur in the cell nucleus. Therefore, the vRNPs must be imported into the nucleus for viral transcription and replication, which requires participation of host proteins. However, the mechanisms of the IAV-host interactions involved in nuclear import remain poorly...

    Qingxia Gao, Cha Yang, Caiyue Ren, Shishuo Zhang, Xiaochen Gao, Meilin Jin, Huanchun Chen, Wenjun Ma, Hongbo Zhou
  • Cytidine Monophosphate <em>N</em>-Acetylneuraminic Acid Synthetase and Solute Carrier Family 35 Member A1 Are Required for Reovirus Binding and Infection
    Virus-Cell Interactions
    Cytidine Monophosphate N-Acetylneuraminic Acid Synthetase and Solute Carrier Family 35 Member A1 Are Required for Reovirus Binding and Infection

    Attachment factors and receptors are important determinants of dissemination and tropism during reovirus-induced disease. In a CRISPR cell survival screen, we discovered two genes, Cmas and Slc35a1, which encode proteins required for sialic acid expression on the cell surface and mediate reovirus infection of microglial cells. This work elucidates host genes that render microglial cells susceptible to reovirus...

    Kelly Urbanek, Danica M. Sutherland, Robert C. Orchard, Craig B. Wilen, Jonathan J. Knowlton, Pavithra Aravamudhan, Gwen M. Taylor, Herbert W. Virgin, Terence S. Dermody
  • Enterovirus Infection Induces Massive Recruitment of All Isoforms of Small Cellular Arf GTPases to the Replication Organelles
    Virus-Cell Interactions | Spotlight
    Enterovirus Infection Induces Massive Recruitment of All Isoforms of Small Cellular Arf GTPases to the Replication Organelles

    Enteroviruses include many known and emerging pathogens, such as poliovirus, enteroviruses 71 and D68, and others. However, licensed vaccines are available only against poliovirus and enterovirus 71, and specific anti-enterovirus therapeutics are lacking. Enterovirus infection induces the massive remodeling of intracellular membranes and the development of specialized domains harboring viral replication complexes, replication organelles...

    Seyedehmahsa Moghimi, Ekaterina Viktorova, Anna Zimina, Tomasz Szul, Elizabeth Sztul, George A. Belov
  • Phosphatidylethanolamine and Phosphatidylserine Synergize To Enhance GAS6/AXL-Mediated Virus Infection and Efferocytosis
    Virus-Cell Interactions | Spotlight
    Phosphatidylethanolamine and Phosphatidylserine Synergize To Enhance GAS6/AXL-Mediated Virus Infection and Efferocytosis

    Phosphatidylserine (PS) and phosphatidylethanolamine (PE) are usually sequestered to the inner leaflet of the plasma membrane of the healthy eukaryotic cells. During apoptosis, these phospholipids move to the cell’s outer leaflet where they are recognized by so-called PS receptors on surveilling phagocytes. Several pathogenic families of enveloped viruses hijack these PS receptors to gain entry into their target cells. Here, we show...

    Lizhou Zhang, Audrey S. Richard, Cody B. Jackson, Amrita Ojha, Hyeryun Choe

Vaccines and Antiviral Agents

  • Enhancement of HIV-1 Env-Specific CD8 T Cell Responses Using Interferon-Stimulated Gene 15 as an Immune Adjuvant
    Vaccines and Antiviral Agents
    Enhancement of HIV-1 Env-Specific CD8 T Cell Responses Using Interferon-Stimulated Gene 15 as an Immune Adjuvant

    Our study described the potential role of ISG15 as an immunomodulatory molecule in the optimization of HIV/AIDS vaccine candidates. Using a DNA prime–MVA boost immunization protocol, our results indicated an increase in the potency and the quality of the HIV-1 Env-specific CD8 T cell response. These results highlight the adjuvant potency of ISG15 to elicit improved viral antigen presentation to the immune system, resulting in an...

    Carmen Elena Gómez, Beatriz Perdiguero, Michela Falqui, María Q. Marín, Martina Bécares, Carlos Óscar S. Sorzano, Juan García-Arriaza, Mariano Esteban, Susana Guerra
  • Open Access
    Priming with DNA Expressing Trimeric HIV V1V2 Alters the Immune Hierarchy Favoring the Development of V2-Specific Antibodies in Rhesus Macaques
    Vaccines and Antiviral Agents
    Priming with DNA Expressing Trimeric HIV V1V2 Alters the Immune Hierarchy Favoring the Development of V2-Specific Antibodies in Rhesus Macaques

    The aim of this work was to design and test a vaccine regimen focusing the immune response on targets associated with infection prevention. We demonstrated that priming with a DNA vaccine expressing only the HIV Env V1V2 region induces Ab responses targeting the critical region in V2 associated with protection. This work shows that V1V2 scaffold DNA priming immunization provides a method to focus immune responses to the desired target...

    Santhi Devasundaram, Margherita Rosati, Antonio Valentin, Svenja Weiss, Vincenza Itri, Hung V. Trinh, Jenifer Bear, Bhabadeb Chowdhury, Celia C. LaBranche, David Montefiori, Guido Ferrari, Mangala Rao, Xiang-Peng Kong, Susan Zolla-Pazner, George N. Pavlakis, Barbara K. Felber
  • Reverse Genetics Approach for Developing Rotavirus Vaccine Candidates Carrying VP4 and VP7 Genes Cloned from Clinical Isolates of Human Rotavirus
    Vaccines and Antiviral Agents
    Reverse Genetics Approach for Developing Rotavirus Vaccine Candidates Carrying VP4 and VP7 Genes Cloned from Clinical Isolates of Human Rotavirus

    Although vaccines have reduced global RV-associated hospitalization and mortality over the past decade, the multisegmented genome of RVs allows reassortment of VP4 and VP7 genes from different RV species and strains. The evolutionary dynamics of novel RV genotypes and their constellations have led to great genomic and antigenic diversity. The reverse genetics system is a powerful tool for manipulating RV genes, thereby controlling viral...

    Yuta Kanai, Misa Onishi, Takahiro Kawagishi, Pimfhun Pannacha, Jeffery A. Nurdin, Ryotaro Nouda, Moeko Yamasaki, Tina Lusiany, Pattara Khamrin, Shoko Okitsu, Satoshi Hayakawa, Hirotaka Ebina, Hiroshi Ushijima, Takeshi Kobayashi
  • A Parainfluenza Virus Vector Expressing the Respiratory Syncytial Virus (RSV) Prefusion F Protein Is More Effective than RSV for Boosting a Primary Immunization with RSV
    Vaccines and Antiviral Agents
    A Parainfluenza Virus Vector Expressing the Respiratory Syncytial Virus (RSV) Prefusion F Protein Is More Effective than RSV for Boosting a Primary Immunization with RSV

    Immune responses to RSV in infants can be reduced due to immunological immaturity and immunosuppression by RSV-specific maternal antibodies. In infants and young children, two infections with wild-type RSV typically are needed to achieve the titers of RSV-specific serum antibodies and protection against illness that are observed in adults. Therefore, a boost might substantially improve the performance of live pediatric RSV vaccines...

    Bo Liang, Yumiko Matsuoka, Cyril Le Nouën, Xueqiao Liu, Richard Herbert, Joanna Swerczek, Celia Santos, Monica Paneru, Peter L. Collins, Ursula J. Buchholz, Shirin Munir
  • Computationally Optimized Broadly Reactive H2 HA Influenza Vaccines Elicited Broadly Cross-Reactive Antibodies and Protected Mice from Viral Challenges
    Vaccines and Antiviral Agents
    Computationally Optimized Broadly Reactive H2 HA Influenza Vaccines Elicited Broadly Cross-Reactive Antibodies and Protected Mice from Viral Challenges

    H2N2 influenza has caused at least one pandemic in the past. Given that individuals born after 1968 have not been exposed to H2N2 influenza viruses, a future pandemic caused by H2 influenza is likely. An effective H2 influenza vaccine would need to elicit broadly cross-reactive antibodies to multiple H2 influenza viruses. Choosing a wild-type virus to create a vaccine may elicit a narrow immune response and not protect against multiple...

    Z. Beau Reneer, Parker J. Jamieson, Amanda L. Skarlupka, Ying Huang, Ted M. Ross
  • Viral Subpopulation Screening Guides in Designing a High Interferon-Inducing Live Attenuated Influenza Vaccine by Targeting Rare Mutations in NS1 and PB2 Proteins
    Vaccines and Antiviral Agents
    Viral Subpopulation Screening Guides in Designing a High Interferon-Inducing Live Attenuated Influenza Vaccine by Targeting Rare Mutations in NS1 and PB2 Proteins

    Effectiveness of NS1-truncated live attenuated influenza vaccines relies heavily on their ability to induce elevated interferon responses in vaccinated hosts. Influenza viruses contain diverse particle subpopulations with distinct phenotypes. We show that live influenza vaccines can contain underappreciated subpopulations with enhanced interferon-inducing phenotypes. The genomic traits of such virus subpopulations can be used to further...

    Amir Ghorbani, Michael C. Abundo, Hana Ji, Kara J. M. Taylor, John M. Ngunjiri, Chang-Won Lee
  • Replication of Small Ruminant Lentiviruses in Aluminum Hydroxide-Induced Granulomas in Sheep: a Potential New Factor for Viral Dissemination
    Vaccines and Antiviral Agents
    Replication of Small Ruminant Lentiviruses in Aluminum Hydroxide-Induced Granulomas in Sheep: a Potential New Factor for Viral Dissemination

    Granulomas are inflammation-derived structures elicited by foreign bodies or certain infections. Aluminum adjuvants included in vaccines induce granulomas in many species. In sheep, these are persistent and consist of activated macrophages. Small ruminant lentiviruses (SRLV), which are macrophage-tropic lentiviruses, cause a chronic wasting disease affecting animal welfare and production. Here, we studied the occurrence of SRLV in...

    Irache Echeverría, Ricardo de Miguel, Javier Asín, Ana Rodríguez-Largo, Antonio Fernández, Marta Pérez, Damián de Andrés, Lluís Luján, Ramsés Reina

Pathogenesis and Immunity

  • The Tegument Protein pUL47 of Marek’s Disease Virus Is Necessary for Horizontal Transmission and Is Important for Expression of Glycoprotein gC
    Pathogenesis and Immunity
    The Tegument Protein pUL47 of Marek’s Disease Virus Is Necessary for Horizontal Transmission and Is Important for Expression of Glycoprotein gC

    Host-to-host transmission of viruses is ideally studied in vivo in the natural host. Veterinary viruses such as Marek’s disease virus (MDV) are, therefore, models of choice to explore these aspects. The natural host of MDV, the chicken, is small, inexpensive, and economically important. MDV is a deadly and contagious herpesvirus that can kill infected animals in less than 4 weeks. The virus naturally infects epithelial cells of...

    Aurélien Chuard, Katia Courvoisier-Guyader, Sylvie Rémy, Stephen Spatz, Caroline Denesvre, David Pasdeloup
  • Open Access
    Simian-Human Immunodeficiency Virus SHIV.C.CH505 Persistence in ART-Suppressed Infant Macaques Is Characterized by Elevated SHIV RNA in the Gut and a High Abundance of Intact SHIV DNA in Naive CD4<sup>+</sup> T Cells
    Pathogenesis and Immunity
    Simian-Human Immunodeficiency Virus SHIV.C.CH505 Persistence in ART-Suppressed Infant Macaques Is Characterized by Elevated SHIV RNA in the Gut and a High Abundance of Intact SHIV DNA in Naive CD4+ T Cells

    Uncovering the sanctuaries of the long-lived HIV-1 reservoir is crucial to develop cure strategies. Pediatric immunity is distinct from that of adults, which may alter where the reservoir is established in infancy. Thus, it is important to utilize pediatric models to inform cure-directed approaches for HIV-1-infected children. We used an infant rhesus macaque model of HIV-1 infection via breastfeeding to identify key sites of viral...

    Veronica Obregon-Perko, Katherine M. Bricker, Gloria Mensah, Ferzan Uddin, Mithra R. Kumar, Emily J. Fray, Robert F. Siliciano, Nils Schoof, Anna Horner, Maud Mavigner, Shan Liang, Thomas Vanderford, Julian Sass, Cliburn Chan, Stella J. Berendam, Katharine J. Bar, George M. Shaw, Guido Silvestri, Genevieve G. Fouda, Sallie R. Permar, Ann Chahroudi

Letter to the Editor

  • Relationships between Neutralization, Binding, and ADCC of Broadly Neutralizing Antibodies against Reservoir HIV
    Letter to the Editor
    Relationships between Neutralization, Binding, and ADCC of Broadly Neutralizing Antibodies against Reservoir HIV
    Yanqin Ren, Maria Korom, Adam R. Ward, Ronald Truong, Dora Chan, Szu-Han Huang, Colin M. Kovacs, Erika Benko, Jeffrey T. Safrit, John Lee, Hermes Garbán, Rebecca Lynch, R. Brad Jones

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Journal of Virology: 95 (2)

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volume 95, issue 2
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  • COVID-19 Vaccines: “Warp Speed” Needs Mind Melds, Not Warped Minds
  • Receptor Recognition by the Novel Coronavirus from Wuhan: an Analysis Based on Decade-Long Structural Studies of SARS Coronavirus
  • Molecular Mechanism for Antibody-Dependent Enhancement of Coronavirus Entry
  • Human Leukocyte Antigen Susceptibility Map for Severe Acute Respiratory Syndrome Coronavirus 2
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