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Table of Contents

April 2019; Volume 93,Issue 7

Spotlight

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

Gem

  • Free
    An Emerging Issue in Oncogenic Virology: the Role of Beta Human Papillomavirus Types in the Development of Cutaneous Squamous Cell Carcinoma
    Gem
    An Emerging Issue in Oncogenic Virology: the Role of Beta Human Papillomavirus Types in the Development of Cutaneous Squamous Cell Carcinoma

    Evidence suggests that beta human papillomaviruses (HPVs), together with ultraviolet radiation, contribute to the development of cutaneous squamous cell carcinoma. Beta HPVs appear to be not the main drivers of carcinogenesis but rather facilitators of the accumulation of ultraviolet-induced DNA mutations.

    Dana E. Rollison, Daniele Viarisio, Rossybelle P. Amorrortu, Tarik Gheit, Massimo Tommasino

Structure and Assembly

  • Residues on Adeno-associated Virus Capsid Lumen Dictate Interactions and Compatibility with the Assembly-Activating Protein
    Structure and Assembly | Spotlight
    Residues on Adeno-associated Virus Capsid Lumen Dictate Interactions and Compatibility with the Assembly-Activating Protein

    Efforts to engineer the AAV capsid to gain desirable properties for gene therapy (e.g., tropism, reduced immunogenicity, and higher potency) require that capsid modifications do not affect particle assembly. The relationship between VP and the cofactor that facilitates its assembly, AAP, is central to both assembly preservation and vector production. Understanding the requirements for this compatibility can inform manufacturing...

    Anna C. Maurer, Ana Karla Cepeda Diaz, Luk H. Vandenberghe
  • Cryo-electron Microscopy Structures of Novel Viruses from Mud Crab <em>Scylla paramamosain</em> with Multiple Infections
    Structure and Assembly
    Cryo-electron Microscopy Structures of Novel Viruses from Mud Crab Scylla paramamosain with Multiple Infections

    Pathogen identification is vital for unknown infectious outbreaks, especially for dual or multiple infections. Sleeping disease (SD) in crabs causes great economic losses to aquaculture worldwide. Here we report the discovery and identification of a novel virus in mud crabs with multiple infections that was not previously detected by molecular, immune, or traditional electron microscopy (EM) methods. High-resolution structures of...

    Yuanzhu Gao, Shanshan Liu, Jiamiao Huang, Qianqian Wang, Kunpeng Li, Jian He, Jianguo He, Shaoping Weng, Qinfen Zhang

Genome Replication and Regulation of Viral Gene Expression

  • Minichromosome Maintenance Proteins Cooperate with LANA during the G<sub>1</sub>/S Phase of the Cell Cycle To Support Viral DNA Replication
    Genome Replication and Regulation of Viral Gene Expression
    Minichromosome Maintenance Proteins Cooperate with LANA during the G1/S Phase of the Cell Cycle To Support Viral DNA Replication

    LANA-mediated latent DNA replication is essential for efficient maintenance of KSHV episomes in the host. During latency, virus relies on the host cellular machinery for replication, which occurs in synchrony with the cellular DNA. LANA interacts with the components of multiple cellular pathways, including cellular replication machinery, and recruits them to the viral origin for DNA replication. In this study, we characterize the...

    Prerna Dabral, Timsy Uppal, Cyprian C. Rossetto, Subhash C. Verma

Genetic Diversity and Evolution

  • Impact of Cultivated Hosts on the Recombination of <em>Cucumber Mosaic Virus</em>
    Genetic Diversity and Evolution
    Impact of Cultivated Hosts on the Recombination of Cucumber Mosaic Virus

    Recombination is an important mechanism used by viruses for their diversification and to adapt to diverse hosts. Understanding the host role in the mechanisms of evolution is important for virus disease management and controlling the emergence of new strains. This study shows the impact that cultivated hosts are playing in the evolution of CMV. Furthermore, our results and previous studies show how some specific hosts could be an ideal...

    Rimnoma S. Ouedraogo, Justin S. Pita, Irenée P. Somda, Oumar Traore, Marilyn J. Roossinck

Virus-Cell Interactions

  • Ceramide Suppresses Influenza A Virus Replication <em>In Vitro</em>
    Virus-Cell Interactions
    Ceramide Suppresses Influenza A Virus Replication In Vitro

    Understanding the effect of sphingolipid metabolism on viral pathogenesis provide important insights into the development of therapeutic strategies against microbial infections. In this study, we demonstrate a critical role of ceramide during influenza A virus infection. We demonstrate that ceramide produced through de novo biosynthesis possess an antiviral role. These observations unlock new opportunities for the development...

    Nadia Soudani, Rouba Hage-Sleiman, Walid Karam, Ghassan Dbaibo, Hassan Zaraket
  • Epigenetic Modification Is Regulated by the Interaction of Influenza A Virus Nonstructural Protein 1 with the <em>De Novo</em> DNA Methyltransferase DNMT3B and Subsequent Transport to the Cytoplasm for K48-Linked Polyubiquitination
    Virus-Cell Interactions
    Epigenetic Modification Is Regulated by the Interaction of Influenza A Virus Nonstructural Protein 1 with the De Novo DNA Methyltransferase DNMT3B and Subsequent Transport to the Cytoplasm for K48-Linked Polyubiquitination

    The nonstructural protein 1 (NS1) of the influenza A virus (IAV) is a multifunctional protein that counters cellular antiviral activities and is a virulence factor. However, the involvement of NS1 in DNA methylation during IAV infection has not been established. Here, we reveal that the NS1 protein binds the cellular DNMT3B DNA methyltransferase, thereby inhibiting the methylation of the promoters of genes encoding suppressors of JAK-...

    Shi Liu, Li Liu, Gang Xu, Zhongying Cao, Qing Wang, Shun Li, Nanfang Peng, Jingchuan Yin, Haisheng Yu, Mengqi Li, Zhangchuan Xia, Li Zhou, Yong Lin, Xueyu Wang, Qian Li, Chengliang Zhu, Xuecheng Yang, Jun Wang, Yinglong She, Mengji Lu, Ying Zhu
  • Chloroviruses Lure Hosts through Long-Distance Chemical Signaling
    Virus-Cell Interactions | Spotlight
    Chloroviruses Lure Hosts through Long-Distance Chemical Signaling

    Viruses have not previously been reported to act as chemotactic/chemoattractive agents. Rather, viruses as extracellular entities are generally viewed as non-metabolically active spore-like agents that await further infection events upon collision with appropriate host cells. That a virus might actively contribute to its fate via chemotaxis and change the behavior of an organism independent of infection is unprecedented.

    ...
    David D. Dunigan, Maitham Al-Sammak, Zeina Al-Ameeli, Irina V. Agarkova, John P. DeLong, James L. Van Etten
  • CD4-Dependent Modulation of HIV-1 Entry by LY6E
    Virus-Cell Interactions
    CD4-Dependent Modulation of HIV-1 Entry by LY6E

    The role of IFN-induced genes (ISGs) in viral infection remains incompletely understood. While most ISGs are antiviral, some ISGs have been shown to promote viral infection, including HIV-1 infection. We previously showed that IFN-inducible LY6E protein promotes HIV-1 infection in human PMBCs and high-CD4-expressing SupT1 cells. Here we found that LY6E inhibits HIV-1 entry and replication in low-CD4-expressing MDMs and Jurkat cells....

    Jingyou Yu, Chen Liang, Shan-Lu Liu
  • Expression of MDM2 in Macrophages Promotes the Early Postentry Steps of HIV-1 Infection through Inhibition of p53
    Virus-Cell Interactions
    Expression of MDM2 in Macrophages Promotes the Early Postentry Steps of HIV-1 Infection through Inhibition of p53

    Macrophages, with their long life span in vivo and their resistance to HIV-1-mediated cytopathic effect, might serve as viral reservoirs, contributing to virus persistence in an infected individual. Identification of host factors that increase the overall susceptibility of macrophages to HIV-1 might provide new therapeutic targets for the efficient control of viral replication in these cells and limit the formation of...

    Yann Breton, Vincent Desrosiers, Michel Ouellet, Alexandre Deshiere, Cynthia Torresilla, Éric A. Cohen, Michel J. Tremblay
  • Adenosine Deaminase Acting on RNA 1 Associates with Orf Virus OV20.0 and Enhances Viral Replication
    Virus-Cell Interactions
    Adenosine Deaminase Acting on RNA 1 Associates with Orf Virus OV20.0 and Enhances Viral Replication

    Viruses evolve specific strategies to counteract host innate immunity. ORFV, an important zoonotic pathogen, encodes OV20.0 to suppress PKR activation via multiple mechanisms, including interactions with PKR and two PKR activators. In this study, we demonstrated that OV20.0 interacts with ADAR1, a cellular enzyme responsible for converting adenosine (A) to inosine (I) in RNA. The RNA binding domains, but not the catalytic domain, of...

    Guan-Ru Liao, Yeu-Yang Tseng, Ching-Yu Tseng, Fong-Yuan Lin, Yumiko Yamada, Hao-Ping Liu, Chih-Ying Kuan, Wei-Li Hsu
  • Open Access
    Equine Herpesvirus 1 Bridles T Lymphocytes To Reach Its Target Organs
    Virus-Cell Interactions
    Equine Herpesvirus 1 Bridles T Lymphocytes To Reach Its Target Organs

    Equine herpesvirus 1 (EHV1) is an ancestral alphaherpesvirus that is related to herpes simplex virus 1 and causes respiratory, reproductive, and neurological disorders in Equidae. EHV1 is indisputably a master at exploiting leukocytes to reach its target organs, accordingly evading the host immunity. However, the role of T lymphocytes in cell-associated viremia remains poorly understood. Here we show that activated T lymphocytes...

    Katrien C. K. Poelaert, Jolien Van Cleemput, Kathlyn Laval, Herman W. Favoreel, Liesbeth Couck, Wim Van den Broeck, Walid Azab, Hans J. Nauwynck
  • The Polar Region of the HIV-1 Envelope Protein Determines Viral Fusion and Infectivity by Stabilizing the gp120-gp41 Association
    Virus-Cell Interactions
    The Polar Region of the HIV-1 Envelope Protein Determines Viral Fusion and Infectivity by Stabilizing the gp120-gp41 Association

    Although extensive studies of the transmembrane unit (gp41) of HIV-1 Env have led to a fusion inhibitor clinically used to block viral entry, the functions of different domains of gp41 in HIV-1 fusion and infectivity are not fully elucidated. The polar region (PR) of gp41 has been proposed to participate in HIV-1 membrane fusion in biochemical analyses, but its role in viral entry and infectivity remain unclear. In our effort to...

    Wuxun Lu, Shuliang Chen, Jingyou Yu, Ryan Behrens, Joshua Wiggins, Nathan Sherer, Shan-Lu Liu, Yong Xiong, Shi-Hua Xiang, Li Wu
  • Mechanism of Tetherin Inhibition of Alphavirus Release
    Virus-Cell Interactions
    Mechanism of Tetherin Inhibition of Alphavirus Release

    The mechanisms of tetherin’s antiviral activities and viral tetherin antagonism have been studied in detail for a number of different viruses. Although viral countermeasures against tetherin can differ significantly, overall, tetherin’s antiviral activity correlates with physical tethering of virus particles to prevent their release. While tetherin can mediate virus endocytic uptake and clearance, this has not been observed to be...

    Judy J. Wan, Yaw Shin Ooi, Margaret Kielian
  • The Nonstructural NS1 Protein of Influenza Viruses Modulates <em>TP53</em> Splicing through Host Factor CPSF4
    Virus-Cell Interactions
    The Nonstructural NS1 Protein of Influenza Viruses Modulates TP53 Splicing through Host Factor CPSF4

    Influenza A viruses (IAV) constitute a major public health issue, causing illness and death in high-risk populations during seasonal epidemics or pandemics. IAV are known to modulate cellular pathways to promote their replication and avoid immune restriction via the targeting of several cellular proteins. One of these proteins, p53, is a master regulator involved in a large panel of biological processes, including cell cycle arrest,...

    Julia Dubois, Aurélien Traversier, Thomas Julien, Blandine Padey, Bruno Lina, Jean-Christophe Bourdon, Virginie Marcel, Guy Boivin, Manuel Rosa-Calatrava, Olivier Terrier
  • Sirtuin 6 Attenuates Kaposi's Sarcoma-Associated Herpesvirus Reactivation by Suppressing Ori-Lyt Activity and Expression of RTA
    Virus-Cell Interactions
    Sirtuin 6 Attenuates Kaposi's Sarcoma-Associated Herpesvirus Reactivation by Suppressing Ori-Lyt Activity and Expression of RTA

    Kaposi’s sarcoma-associated herpesvirus (KSHV) is a pathogen causing cancer in the immune-deficient population. The reactivation of KSHV from latency is important for it to be carcinogenic. Our finding that SIRT6 has inhibitory effects on KSHV reactivation by interacting with the viral genome and suppressing viral gene expression is important because it might lead to a strategy of interfering with KSHV reactivation. Overexpression of...

    Min Hu, Najealicka Armstrong, Edward Seto, Wenwei Li, Fanxiu Zhu, Paul C. Wang, Qiyi Tang
  • Acetylation of E2 by P300 Mediates Topoisomerase Entry at the Papillomavirus Replicon
    Virus-Cell Interactions
    Acetylation of E2 by P300 Mediates Topoisomerase Entry at the Papillomavirus Replicon

    Human papillomaviruses affect an estimated 75% of the sexually active adult population in the United States, with 5.5 million new cases emerging every year. More than 200 HPV genotypes have been identified; a subset of them are linked to the development of cancers from these epithelial infections. Specific antiviral medical treatments for infected individuals are not available. This project examines the mechanisms that control viral...

    Yanique Thomas, Elliot J. Androphy
  • Open Access
    Engineering Responses to Amino Acid Substitutions in the VP0- and VP3-Coding Regions of PanAsia-1 Strains of Foot-and-Mouth Disease Virus Serotype O
    Virus-Cell Interactions
    Engineering Responses to Amino Acid Substitutions in the VP0- and VP3-Coding Regions of PanAsia-1 Strains of Foot-and-Mouth Disease Virus Serotype O

    The sequence variation within the capsid proteins occurs frequently in the infection of susceptible tissue cultures, reflecting the high levels of genetic diversity of FMDV. A systematic study for the functional significance of isolate-specific residues in VP0 and VP3 of FMDV PanAsia-1 strains suggested that the interaction of amino acid side chains between the N terminus of VP4 and several potential domains of VP1-3 had cascading...

    Xing-Wen Bai, Hui-Fang Bao, Ping-Hua Li, Xue-Qing Ma, Pu Sun, Qi-Feng Bai, Meng Zhang, Hong Yuan, Dong-Dong Chen, Kun Li, Ying-Li Chen, Yi-Mei Cao, Yuan-Fang Fu, Jing Zhang, Dong Li, Zeng-Jun Lu, Zai-Xin Liu, Jian-Xun Luo

Cellular Response to Infection

  • HoxA10 Facilitates SHP-1-Catalyzed Dephosphorylation of p38 MAPK/STAT3 To Repress Hepatitis B Virus Replication by a Feedback Regulatory Mechanism
    Cellular Response to Infection
    HoxA10 Facilitates SHP-1-Catalyzed Dephosphorylation of p38 MAPK/STAT3 To Repress Hepatitis B Virus Replication by a Feedback Regulatory Mechanism

    Two billion people have been infected with HBV worldwide; about 240 million infected patients developed chronic hepatitis B (CHB), and 650,000 die each year from liver cirrhosis (LC) or hepatocellular carcinoma (HCC). This work elucidates a mechanism underlying the control of HBV replication. HBV infection activates HoxA10, a regulator of cell differentiation and cancer progression, in human cells and patients with CHB and HCC. HoxA10...

    Qingyu Yang, Qi Zhang, Xuewu Zhang, Lei You, Wenbiao Wang, Weiyong Liu, Yang Han, Chunqiang Ma, Wei Xu, Junbo Chen, Hua Yang, Pin Wan, Yao Zhou, Yingle Liu, Kailang Wu, Ziwen Yang, Jianguo Wu
  • Biological and Molecular Characterization of Chenopodium quinoa Mitovirus 1 Reveals a Distinct Small RNA Response Compared to Those of Cytoplasmic RNA Viruses
    Cellular Response to Infection | Spotlight
    Biological and Molecular Characterization of Chenopodium quinoa Mitovirus 1 Reveals a Distinct Small RNA Response Compared to Those of Cytoplasmic RNA Viruses

    This paper reports the first biological characterization of a bona fide plant mitovirus in an important crop, Chenopodium quinoa, providing data supporting that mitoviruses have the typical features of cryptic (persistent) plant viruses. We, for the first time, demonstrate that plant mitoviruses are associated with mitochondria in plants. In contrast to...

    L. Nerva, G. Vigani, D. Di Silvestre, M. Ciuffo, M. Forgia, W. Chitarra, M. Turina
  • GADD45γ Activated Early in the Course of Herpes Simplex Virus 1 Infection Suppresses the Activation of a Network of Innate Immunity Genes
    Cellular Response to Infection
    GADD45γ Activated Early in the Course of Herpes Simplex Virus 1 Infection Suppresses the Activation of a Network of Innate Immunity Genes

    Previous studies from our laboratory reported that knockout of some innate immunity genes was associated with increases in the expression of overlapping networks of genes and significant loss of the ability to support the replication of HSV-1; knockout of other genes was associated with decreases in the expression of overlapping networks of genes and had no effect on virus replication. In this report, we document that depletion of...

    Mingmin She, Haifang Jiang, Xiaoxiang Chen, Xiaoqing Chen, Xianjie Liu, Xueyan Zhang, Bernard Roizman, Grace G. Zhou

Vaccines and Antiviral Agents

  • Potent Anti-hepatitis C Virus (HCV) T Cell Immune Responses Induced in Mice Vaccinated with DNA-Launched RNA Replicons and Modified Vaccinia Virus Ankara-HCV
    Vaccines and Antiviral Agents
    Potent Anti-hepatitis C Virus (HCV) T Cell Immune Responses Induced in Mice Vaccinated with DNA-Launched RNA Replicons and Modified Vaccinia Virus Ankara-HCV

    HCV represents a global health problem as more than 71 million people are chronically infected worldwide. Direct-acting antiviral agents can cure HCV infection in most patients, but due to the high cost of these agents and the emergence of resistant mutants, they do not represent a feasible and affordable strategy to eradicate the virus. Therefore, a vaccine is an urgent goal that requires efforts to understand the correlates of...

    María Q. Marín, Patricia Pérez, Karl Ljungberg, Carlos Óscar S. Sorzano, Carmen E. Gómez, Peter Liljeström, Mariano Esteban, Juan García-Arriaza
  • Open Access
    Antigenicity and Immunogenicity of Differentially Glycosylated Hepatitis C Virus E2 Envelope Proteins Expressed in Mammalian and Insect Cells
    Vaccines and Antiviral Agents
    Antigenicity and Immunogenicity of Differentially Glycosylated Hepatitis C Virus E2 Envelope Proteins Expressed in Mammalian and Insect Cells

    The development of a vaccine for hepatitis C virus (HCV) remains a global health challenge. A major challenge for vaccine development is focusing the immune response on conserved regions of the HCV envelope protein, E2, capable of eliciting neutralizing antibodies. Modification of E2 by glycosylation might influence the immunogenicity of E2. Accordingly, we performed molecular and immunogenic comparisons of E2 produced in mammalian and...

    Richard A. Urbanowicz, Ruixue Wang, John E. Schiel, Zhen-yong Keck, Melissa C. Kerzic, Patrick Lau, Sneha Rangarajan, Kyle J. Garagusi, Lei Tan, Johnathan D. Guest, Jonathan K. Ball, Brian G. Pierce, Roy A. Mariuzza, Steven K. H. Foung, Thomas R. Fuerst
  • Clade C HIV-1 Envelope Vaccination Regimens Differ in Their Ability To Elicit Antibodies with Moderate Neutralization Breadth against Genetically Diverse Tier 2 HIV-1 Envelope Variants
    Vaccines and Antiviral Agents
    Clade C HIV-1 Envelope Vaccination Regimens Differ in Their Ability To Elicit Antibodies with Moderate Neutralization Breadth against Genetically Diverse Tier 2 HIV-1 Envelope Variants

    Despite much progress, we still do not have a clear understanding of how to elicit a protective neutralizing antibody response against HIV-1 through vaccination. There have been great strides in the development of envelope immunogens that mimic the virus particle, but less is known about how different vaccination modalities and adjuvants contribute to shaping the antibody response. We compared seven different vaccines that were...

    Samantha Burton, Lori M. Spicer, Tysheena P. Charles, Sailaja Gangadhara, Pradeep B. J. Reddy, Tiffany M. Styles, Vijayakumar Velu, Sudhir Pai Kasturi, Traci Legere, Eric Hunter, Bali Pulendran, Rama Amara, Peter Hraber, Cynthia A. Derdeyn
  • Effects of Alterations to the CX3C Motif and Secreted Form of Human Respiratory Syncytial Virus (RSV) G Protein on Immune Responses to a Parainfluenza Virus Vector Expressing the RSV G Protein
    Vaccines and Antiviral Agents
    Effects of Alterations to the CX3C Motif and Secreted Form of Human Respiratory Syncytial Virus (RSV) G Protein on Immune Responses to a Parainfluenza Virus Vector Expressing the RSV G Protein

    Human RSV is the leading viral cause of severe pediatric respiratory illness. An RSV vaccine is not yet available. The RSV attachment protein G is an important protective and neutralization antigen. G contains a conserved fractalkine-like CX3C motif and is expressed in mG and sG forms. sG and the CX3C motif are thought to interfere with host immune responses, but this remains poorly characterized. Here, we used an attenuated chimeric...

    Bo Liang, Barbora Kabatova, Juraj Kabat, David W. Dorward, Xiang Liu, Sonja Surman, Xueqiao Liu, Annie Park Moseman, Ursula J. Buchholz, Peter L. Collins, Shirin Munir
  • Reduction of Kaposi’s Sarcoma-Associated Herpesvirus Latency Using CRISPR-Cas9 To Edit the Latency-Associated Nuclear Antigen Gene
    Vaccines and Antiviral Agents
    Reduction of Kaposi’s Sarcoma-Associated Herpesvirus Latency Using CRISPR-Cas9 To Edit the Latency-Associated Nuclear Antigen Gene

    The ability for Kaposi’s sarcoma-associated herpesvirus (KSHV), the causative agent of Kaposi’s sarcoma (KS), to establish and maintain latency has been a major challenge to clearing infection and preventing KS development. This is the first study to demonstrate the feasibility of using a KSHV LANA-targeted CRISPR-Cas9 and adenoviral delivery system to disrupt KSHV latency in infected epithelial and endothelial cell lines. Our system...

    For Yue Tso, John T. West, Charles Wood
  • Validating Enterovirus D68-2A<sup>pro</sup> as an Antiviral Drug Target and the Discovery of Telaprevir as a Potent D68-2A<sup>pro</sup> Inhibitor
    Vaccines and Antiviral Agents | Spotlight
    Validating Enterovirus D68-2Apro as an Antiviral Drug Target and the Discovery of Telaprevir as a Potent D68-2Apro Inhibitor

    A 2014 EV-D68 outbreak in the United States has been linked to the development of acute flaccid myelitis in children. Unfortunately, no treatment options against EV-D68 are currently available, and the development of effective therapeutics is urgently needed. Here, we characterize and validate a new EV-D68 drug target, the 2Apro, and identify telaprevir—an FDA-approved drug used to treat hepatitis C virus (HCV) infections—as...

    Rami Musharrafieh, Chunlong Ma, Jiantao Zhang, Yanmei Hu, Jessica M. Diesing, Michael T. Marty, Jun Wang

Pathogenesis and Immunity

  • Porcine Circovirus Type 2 Induces ORF3-Independent Mitochondrial Apoptosis via PERK Activation and Elevation of Cytosolic Calcium
    Pathogenesis and Immunity
    Porcine Circovirus Type 2 Induces ORF3-Independent Mitochondrial Apoptosis via PERK Activation and Elevation of Cytosolic Calcium

    PCV2 encodes protein ORF3, a putative protein with proapoptotic activity. Our early studies showed that PCV2 infection triggers ER stress via selective activation of the PERK pathway, a branch of the ER stress pathways, in permissive cells for enhanced replication and infection increased cytosolic Ca2+ and ROS levels. Here we clearly show that PCV2 infection or Cap expression induces ORF3-independent apoptosis via increased...

    Yikai Zhang, Renjie Sun, Shichao Geng, Ying Shan, Xiaoliang Li, Weihuan Fang
  • Identification of NK Cell Subpopulations That Differentiate HIV-Infected Subject Cohorts with Diverse Levels of Virus Control
    Pathogenesis and Immunity | Spotlight
    Identification of NK Cell Subpopulations That Differentiate HIV-Infected Subject Cohorts with Diverse Levels of Virus Control

    HIV infection results in the establishment of a stable reservoir of latently infected cells; ART is usually required to keep viral replication under control and disease progression at bay, though a small subset of HIV-infected subjects can control HIV infection without ART through immunological mechanisms. In this study, we sought to identify subpopulations of NK cells that may be involved in the natural immunological control of HIV...

    Christopher W. Pohlmeyer, Veronica D. Gonzalez, Alivelu Irrinki, Ricardo N. Ramirez, Li Li, Andrew Mulato, Jeffrey P. Murry, Aaron Arvey, Rebecca Hoh, Steven G. Deeks, George Kukolj, Tomas Cihlar, Stefan Pflanz, Garry P. Nolan, Gundula Min-Oo
  • Pathogenesis, Host Innate Immune Response, and Aerosol Transmission of Influenza D Virus in Cattle
    Pathogenesis and Immunity
    Pathogenesis, Host Innate Immune Response, and Aerosol Transmission of Influenza D Virus in Cattle

    Influenza D virus (IDV), a new genus of the Orthomyxoviridae family, has a broad geographical distribution and can infect several animal species. Cattle are so far considered the primary host for IDV, but the pathogenicity and the prevalence of this virus are still unclear. We demonstrated that under experimental conditions (in a controlled environment and in the absence of coinfecting pathogens), IDV is able to cause mild to...

    Elias Salem, Sara Hägglund, Hervé Cassard, Tifenn Corre, Katarina Näslund, Charlotte Foret, David Gauthier, Anne Pinard, Maxence Delverdier, Siamak Zohari, Jean-François Valarcher, Mariette Ducatez, Gilles Meyer
  • Transmission of a Novel Genotype of Hepatitis E Virus from Bactrian Camels to Cynomolgus Macaques
    Pathogenesis and Immunity
    Transmission of a Novel Genotype of Hepatitis E Virus from Bactrian Camels to Cynomolgus Macaques

    It is estimated that one-third of the world population have been exposed to hepatitis E virus (HEV). In developed countries and China, zoonotic HEV strains are responsible for almost all acute and chronic HEV infection cases. It is always of immediate interest to investigate the zoonotic potential of novel HEV strains. In 2016, we discovered a novel HEV genotype, HEV8, in Bactrian camels, but the epidemiology, zoonotic potential, and...

    Lin Wang, Jade L. L. Teng, Susanna K. P. Lau, Siddharth Sridhar, Hongwei Fu, Wanyun Gong, Manyu Li, Qieshi Xu, Yunye He, Hui Zhuang, Patrick C. Y. Woo, Ling Wang
  • The Carboxyl Terminus of Tegument Protein pUL21 Contributes to Pseudorabies Virus Neuroinvasion
    Pathogenesis and Immunity
    The Carboxyl Terminus of Tegument Protein pUL21 Contributes to Pseudorabies Virus Neuroinvasion

    Herpesviruses are a group of DNA viruses that infect both humans and animals. Alphaherpesviruses are distinguished by their ability to establish latent infection in peripheral neurons. After entering neurons, the herpesvirus capsid interacts with cellular motor proteins and undergoes retrograde transport on axon microtubules. This elaborate process is vital to the herpesvirus lifecycle, but the underlying mechanism remains poorly...

    Kai Yan, Jie Liu, Xiang Guan, Yi-Xin Yin, Hui Peng, Huan-Chun Chen, Zheng-Fei Liu
  • Open Access
    Rare Detection of Antiviral Functions of Polyclonal IgA Isolated from Plasma and Breast Milk Compartments in Women Chronically Infected with HIV-1
    Pathogenesis and Immunity
    Rare Detection of Antiviral Functions of Polyclonal IgA Isolated from Plasma and Breast Milk Compartments in Women Chronically Infected with HIV-1

    Antibodies within the mucosa are part of the first line of defense against mucosal pathogens. Evaluating mucosal antibody isotypes, specificities, and antiviral functions in relationship to the systemic antibody profile can provide insights into whether the antibody response is coordinated in response to mucosal pathogens. In a natural immunity cohort of HIV-infected lactating women, we mapped the fine specificity and function of IgA in...

    Matthew Zirui Tay, Erika L. Kunz, Aaron Deal, Lu Zhang, Kelly E. Seaton, Wes Rountree, Joshua A. Eudailey, Jack Heptinstall, Michael D. McRaven, Edgar Matias, Erin McGuire, Nicole L. Yates, Lautaro G. Perez, David C. Montefiori, R. Glenn Overman, Thomas J. Hope, Xiaoying Shen, Linda Kalilani, Genevieve G. Fouda, Georgia D. Tomaras, Sallie R. Permar
  • Expression of the Pseudorabies Virus gB Glycoprotein Triggers NK Cell Cytotoxicity and Increases Binding of the Activating NK Cell Receptor PILRβ
    Pathogenesis and Immunity
    Expression of the Pseudorabies Virus gB Glycoprotein Triggers NK Cell Cytotoxicity and Increases Binding of the Activating NK Cell Receptor PILRβ

    Natural killer (NK) cells display a prominent cytolytic activity against virus-infected cells and are indispensable in the innate antiviral response, particularly against herpesviruses. Despite their importance in the control of alphaherpesvirus infections, relatively little is known about the mechanisms that trigger NK cell cytotoxicity against alphaherpesvirus-infected cells. Here, using the porcine alphaherpesvirus pseudorabies virus...

    Steffi De Pelsmaeker, Evelien Dierick, Barbara Klupp, Thomas C. Mettenleiter, Claudia Cantoni, Massimo Vitale, Herman W. Favoreel
  • Open Access
    Effective Suppression of HIV-1 Replication by Cytotoxic T Lymphocytes Specific for Pol Epitopes in Conserved Mosaic Vaccine Immunogens
    Pathogenesis and Immunity
    Effective Suppression of HIV-1 Replication by Cytotoxic T Lymphocytes Specific for Pol Epitopes in Conserved Mosaic Vaccine Immunogens

    It is likely necessary for an effective AIDS vaccine to elicit CD8+ T cells with the ability to recognize circulating HIV-1 and suppress its replication. We recently developed novel bivalent mosaic T-cell vaccine immunogens composed of conserved regions of the Gag and Pol proteins matched to at least 80% globally circulating HIV-1 isolates. Nevertheless, it remains to be proven if vaccination with these immunogens can elicit...

    Chengcheng Zou, Hayato Murakoshi, Nozomi Kuse, Tomohiro Akahoshi, Takayuki Chikata, Hiroyuki Gatanaga, Shinichi Oka, Tomáš Hanke, Masafumi Takiguchi

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Journal of Virology: 93 (7)

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volume 93, issue 7
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  • Nonsteroidal Anti-inflammatory Drugs Dampen the Cytokine and Antibody Response to SARS-CoV-2 Infection
  • Receptor Recognition by the Novel Coronavirus from Wuhan: an Analysis Based on Decade-Long Structural Studies of SARS Coronavirus
  • The Nucleocapsid Protein of SARS–CoV-2: a Target for Vaccine Development
  • COVID-19 Vaccines: “Warp Speed” Needs Mind Melds, Not Warped Minds
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