Herpes Simplex Virus 1 γ134.5 Protein Inhibits STING Activation That Restricts Viral Replication.

Abstract:

:The γ134.5 gene of herpes simplex virus 1 (HSV-1) encodes a virulence factor that promotes viral pathogenesis. Although it perturbs TANK-binding kinase 1 (TBK1) in the complex network of innate immune pathways, the underlying mechanism is obscure. Here we report that HSV-1 γ134.5 targets stimulator of interferon genes (STING) in the intracellular DNA recognition pathway that regulates TBK1 activation. In virus-infected cells the γ134.5 protein associates with and inactivates STING, which leads to downregulation of interferon regulatory factor 3 (IRF3) and IFN responses. Importantly, HSV-1 γ134.5 disrupts translocation of STING from the endoplasmic reticulum to Golgi apparatus, a process necessary to prime cellular immunity. Deletion of γ134.5 or its amino-terminal domain from HSV-1 abolishes the observed inhibitory activities. Consistently, an HSV mutant that lacks functional γ134.5 replicated less efficiently in STING+/+ than in STING-/- mouse embryonic fibroblasts. Moreover, reconstituted expression of human STING in the STING-/- cells activated IRF3 and reduced viral growth. These results suggest that control of the DNA sensing pathway by γ134.5 is advantageous to HSV infection.IMPORTANCE Viral inhibition of innate immunity contributes to herpes simplex virus pathogenesis. Although this complex process involves multiple factors, the underlying events remain unclear. We demonstrate that an HSV virulence factor γ134.5 precludes the activation of STING, a central adaptor in the intracellular DNA sensing pathway. Upon HSV infection, this viral protein engages with and inactivates STING. Consequently, it compromises host immunity and facilitates HSV replication. These observations uncover an HSV mechanism that is likely to mediate viral virulence.

journal_name

J Virol

journal_title

Journal of virology

authors

Pan S,Liu X,Ma Y,Cao Y,He B

doi

10.1128/JVI.01015-18

subject

Has Abstract

pub_date

2018-09-26 00:00:00

issue

20

eissn

0022-538X

issn

1098-5514

pii

JVI.01015-18

journal_volume

92

pub_type

杂志文章
  • Structure and formation of circular dimers of simian virus 40 DNA.

    abstract::Most of the viral DNA extracted from simian virus 40 (SV40)-infected African green monkey kidney cells consists of circular molecules about 5.3 kilobases in contour length. However, about 1% of the viral DNA was found to occur as closed circular dimers that appeared to be formed, preferentially, late in infection. The...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.24.1.295-302.1977

    authors: Goff SP,Berg P

    更新日期:1977-10-01 00:00:00

  • Distinct human immunodeficiency virus type 1 subtype A virus circulating in West Africa: sub-subtype A3.

    abstract::Phylogenetic analyses demonstrate significant diversity in worldwide circulating strains of human immunodeficiency virus type 1 (HIV-1). Detailed studies have revealed a complex pattern of intersubtype recombinations, as well as evidence of sub-subtypes circulating in various populations. In this study, we characteriz...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.78.22.12438-12445.2004

    authors: Meloni ST,Kim B,Sankalé JL,Hamel DJ,Tovanabutra S,Mboup S,McCutchan FE,Kanki PJ

    更新日期:2004-11-01 00:00:00

  • Biphasic recruitment of transcriptional repressors to the murine cytomegalovirus major immediate-early promoter during the course of infection in vivo.

    abstract::Our previous studies showed that establishment of murine cytomegalovirus (MCMV) latency in vivo is associated with repression of immediate-early gene expression, deacetylation of histones bound to the major immediate-early promoter (MIEP), changes in patterns of methylation of histones, and recruitment of cellular rep...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.02380-09

    authors: Liu XF,Yan S,Abecassis M,Hummel M

    更新日期:2010-04-01 00:00:00

  • Treatment of transmissible spongiform encephalopathy by intraventricular drug infusion in animal models.

    abstract::The therapeutic efficacy of direct drug infusion into the brain, the target organ of transmissible spongiform encephalopathies, was assessed in transgenic mice intracerebrally infected with 263K scrapie agent. Pentosan polysulfate (PPS) gave the most dramatic prolongation of the incubation period, and amphotericin B h...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/jvi.78.10.4999-5006.2004

    authors: Doh-ura K,Ishikawa K,Murakami-Kubo I,Sasaki K,Mohri S,Race R,Iwaki T

    更新日期:2004-05-01 00:00:00

  • Expression of polyomavirus virion proteins by a vaccinia virus vector: association of VP1 and VP2 with the nuclear framework.

    abstract::The polyomavirus proteins VP1, VP2, and VP3 move from their cytoplasmic site of synthesis into the nucleus, where virus assembly occurs. To identify cellular or viral components which might control this process, we determined the distribution of VP1, VP2, and VP3 in a soluble fraction, a cytoplasmic cytoskeleton fract...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.61.2.516-525.1987

    authors: Stamatos NM,Chakrabarti S,Moss B,Hare JD

    更新日期:1987-02-01 00:00:00

  • Adaptation of a genotype 3 hepatitis E virus to efficient growth in cell culture depends on an inserted human gene segment acquired by recombination.

    abstract::An infectious cDNA clone of a genotype 3 strain of hepatitis E virus adapted to growth in HepG2/C3A human hepatoma cells was constructed. This virus was unusual in that the hypervariable region of the adapted virus contained a 171-nucleotide insertion that encoded 58 amino acids of human S17 ribosomal protein. Analyse...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.00146-12

    authors: Shukla P,Nguyen HT,Faulk K,Mather K,Torian U,Engle RE,Emerson SU

    更新日期:2012-05-01 00:00:00

  • Elicitation of Protective Antibodies against 20 Years of Future H3N2 Cocirculating Influenza Virus Variants in Ferrets Preimmune to Historical H3N2 Influenza Viruses.

    abstract::The vast majority of people already have preexisting immune responses to influenza viruses from one or more subtypes. However, almost all preclinical studies evaluate new influenza vaccine candidates in immunologically naive animals. Recently, our group demonstrated that priming naive ferrets with broadly reactive H1 ...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.00946-18

    authors: Allen JD,Jang H,DiNapoli J,Kleanthous H,Ross TM

    更新日期:2019-01-17 00:00:00

  • Reovirus-induced alteration in expression of apoptosis and DNA repair genes with potential roles in viral pathogenesis.

    abstract::Reoviruses are a leading model for understanding cellular mechanisms of virus-induced apoptosis. Reoviruses induce apoptosis in multiple cell lines in vitro, and apoptosis plays a key role in virus-induced tissue injury of the heart and brain in vivo. The activation of transcription factors NF-kappaB and c-Jun are key...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/jvi.77.16.8934-8947.2003

    authors: DeBiasi RL,Clarke P,Meintzer S,Jotte R,Kleinschmidt-Demasters BK,Johnson GL,Tyler KL

    更新日期:2003-08-01 00:00:00

  • Pandemic H1N1 2009 influenza A virus induces weak cytokine responses in human macrophages and dendritic cells and is highly sensitive to the antiviral actions of interferons.

    abstract::In less than 3 months after the first cases of swine origin 2009 influenza A (H1N1) virus infections were reported from Mexico, WHO declared a pandemic. The pandemic virus is antigenically distinct from seasonal influenza viruses, and the majority of human population lacks immunity against this virus. We have studied ...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.01619-09

    authors: Osterlund P,Pirhonen J,Ikonen N,Rönkkö E,Strengell M,Mäkelä SM,Broman M,Hamming OJ,Hartmann R,Ziegler T,Julkunen I

    更新日期:2010-02-01 00:00:00

  • Oncogenic activity of Epstein-Barr virus latent membrane protein 1 (LMP-1) is down-regulated by lytic LMP-1.

    abstract::The Epstein-Barr virus (EBV) is an oncogenic human herpesvirus. EBV latent membrane protein 1 (LMP-1) is a viral oncogene that manifests its oncogenic phenotype through activation of cellular signaling pathways involved in cell growth, survival, differentiation, and transformation. Lytic LMP-1 (lyLMP-1) is a related E...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.00180-06

    authors: Pandya J,Walling DM

    更新日期:2006-08-01 00:00:00

  • Analysis of T antigen and viral DNA in mouse cells transformed by K virus, a nononcogenic murine papovavirus.

    abstract::A tumorigenic line of mouse cells transformed by the nononcogenic murine K papovavirus was established and characterized. Tumor-bearing animals produced antibody specific for K virus-transformed cells; the K virus T antiserum did not react with polyomavirus-transformed cells. Immunoprecipitation of the T antigen in th...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.50.3.954-956.1984

    authors: Kanda T,Takemoto KK

    更新日期:1984-06-01 00:00:00

  • Differential effects of human immunodeficiency virus type 1 Vpu on the stability of BST-2/tetherin.

    abstract::BST-2/CD317/tetherin is a host factor that inhibits the release of HIV-1 and other unrelated viruses. A current model proposes that BST-2 physically tethers virions to the surface of virus-producing cells. The HIV-1-encoded Vpu protein effectively antagonizes the activity of BST-2. How Vpu accomplishes this task remai...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.02080-10

    authors: Andrew AJ,Miyagi E,Strebel K

    更新日期:2011-03-01 00:00:00

  • Classical swine fever virus can remain virulent after specific elimination of the interferon regulatory factor 3-degrading function of Npro.

    abstract::Pestiviruses prevent alpha/beta interferon (IFN-alpha/beta) production by promoting proteasomal degradation of interferon regulatory factor 3 (IRF3) by means of the viral N(pro) nonstructural protein. N(pro) is also an autoprotease, and its amino-terminal coding sequence is involved in translation initiation. We previ...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.01509-08

    authors: Ruggli N,Summerfield A,Fiebach AR,Guzylack-Piriou L,Bauhofer O,Lamm CG,Waltersperger S,Matsuno K,Liu L,Gerber M,Choi KH,Hofmann MA,Sakoda Y,Tratschin JD

    更新日期:2009-01-01 00:00:00

  • Cellular target genes of Epstein-Barr virus nuclear antigen 2.

    abstract::Epstein-Barr virus (EBV) nuclear antigen 2 (EBNA-2) is a key determinant in the EBV-driven B-cell growth transformation process. By activating an array of viral and cellular target genes, EBNA-2 initiates a cascade of events which ultimately cause cell cycle entry and the proliferation of the infected B cell. In order...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.00665-06

    authors: Maier S,Staffler G,Hartmann A,Höck J,Henning K,Grabusic K,Mailhammer R,Hoffmann R,Wilmanns M,Lang R,Mages J,Kempkes B

    更新日期:2006-10-01 00:00:00

  • Benefits and Perils of Necroptosis in Influenza Virus Infection.

    abstract::Influenza A viruses (IAV) are lytic viruses that have recently been found to activate necroptosis in many of the cell types they infect. Necroptotic cell death is potently immunogenic and limits IAV spread by directly eliminating infected cells and by mobilizing both innate and adaptive immune responses. The benefits ...

    journal_title:Journal of virology

    pub_type: 杂志文章,评审

    doi:10.1128/JVI.01101-19

    authors: Balachandran S,Rall GF

    更新日期:2020-04-16 00:00:00

  • Nasal immunization of mice with virus-like particles protects offspring against rotavirus diarrhea.

    abstract::Rotavirus is the major cause of diarrhea among young infants in both humans and animals. Immune protection of newborns by vaccination is difficult to achieve since there is not enough time to mount an immune response before exposure to the virus. We have designed a vaccination strategy mediating transfer of neutralizi...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/jvi.74.19.8966-8971.2000

    authors: Coste A,Sirard JC,Johansen K,Cohen J,Kraehenbuhl JP

    更新日期:2000-10-01 00:00:00

  • Simian immunodeficiency virus SIVmac239 infection of major histocompatibility complex-identical cynomolgus macaques from Mauritius.

    abstract::Nonhuman primates are widely used to study correlates of protective immunity in AIDS research. Successful cellular immune responses have been difficult to identify because heterogeneity within macaque major histocompatibility complex (MHC) genes results in quantitative and qualitative differences in immune responses. ...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.01841-06

    authors: Wiseman RW,Wojcechowskyj JA,Greene JM,Blasky AJ,Gopon T,Soma T,Friedrich TC,O'Connor SL,O'Connor DH

    更新日期:2007-01-01 00:00:00

  • Kaposi's Sarcoma-Associated Herpesvirus LANA-Adjacent Regions with Distinct Functions in Episome Segregation or Maintenance.

    abstract::Kaposi's sarcoma-associated herpesvirus (KSHV) latency-associated nuclear antigen (LANA) is a 1,162-amino-acid protein that mediates episome persistence of viral genomes. LANA binds the KSHV terminal-repeat (TR) sequence through its carboxy-terminal domain to mediate DNA replication. LANA simultaneously binds mitotic ...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.02158-18

    authors: Juillard F,De León Vázquez E,Tan M,Li S,Kaye KM

    更新日期:2019-03-05 00:00:00

  • Truncated particles produced in fish surviving infectious hematopoietic necrosis virus infection: mediators of persistence?

    abstract::Infectious hematopoietic necrosis virus (IHNV) is a rhabdovirus that produces an acute, lethal infection in rainbow trout (Oncorhynchus mykiss). Fish that survive infection cease to produce detectable infectious virus at approximately 46 days after infection, yet there is evidence that survivor fish continue to harbor...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.73.1.843-849.1999

    authors: Kim CH,Dummer DM,Chiou PP,Leong JA

    更新日期:1999-01-01 00:00:00

  • Internalization of echovirus 1 in caveolae.

    abstract::Echovirus 1 (EV1) is a human pathogen which belongs to the Picornaviridae family of RNA viruses. We have analyzed the early events of infection after EV1 binding to its receptor alpha 2 beta 1 integrin and elucidated the route by which EV1 gains access to the host cell. EV1 binding onto the cell surface and subsequent...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/jvi.76.4.1856-1865.2002

    authors: Marjomäki V,Pietiäinen V,Matilainen H,Upla P,Ivaska J,Nissinen L,Reunanen H,Huttunen P,Hyypiä T,Heino J

    更新日期:2002-02-01 00:00:00

  • N-Linked Glycans and K147 Residue on Hemagglutinin Synergize To Elicit Broadly Reactive H1N1 Influenza Virus Antibodies.

    abstract::Vaccination is the most effective way to prevent influenza virus infections. However, the diversity of antigenically distinct isolates is a challenge for vaccine development. In order to overcome the antigenic variability and improve the protective efficacy of influenza vaccines, our research group has pioneered the d...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.01432-19

    authors: Huang Y,Owino SO,Crevar CJ,Carter DM,Ross TM

    更新日期:2020-02-28 00:00:00

  • T cells expressing the gamma delta T-cell receptor potentiate coxsackievirus B3-induced myocarditis.

    abstract::Initial studies determined whether intraperitoneal (i.p.) injection of BALB/c mice with 0.1, 1.0, and 10 mg of adriamycin (a cardiotoxic anthracycline antibiotic) for times ranging between 1 and 9 weeks prior to i.p. injection of 10(5) PFU of coxsackievirus B3 (CVB3) would alter the severity of virus-induced myocardit...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.66.11.6541-6546.1992

    authors: Huber SA,Moraska A,Choate M

    更新日期:1992-11-01 00:00:00

  • Downregulation of CD4 by human immunodeficiency virus type 1 Nef is dependent on clathrin and involves direct interaction of Nef with the AP2 clathrin adaptor.

    abstract::Nef, an accessory protein of human and simian immunodeficiency viruses, is a critical determinant of pathogenesis that promotes the progression from infection to AIDS. The pathogenic effects of Nef are in large part dependent on its ability to downregulate the macrophage and T-cell coreceptor, CD4. It has been propose...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.02725-06

    authors: Chaudhuri R,Lindwasser OW,Smith WJ,Hurley JH,Bonifacino JS

    更新日期:2007-04-01 00:00:00

  • Host response to the attenuated poxvirus vector NYVAC: upregulation of apoptotic genes and NF-kappaB-responsive genes in infected HeLa cells.

    abstract::NYVAC has been engineered as a safe, attenuated vaccinia virus (VV) vector for use in vaccination against a broad spectrum of pathogens and tumors. Due to the interest in NYVAC-based vectors as vaccines and current phase I/II clinical trials with this vector, there is a need to analyze the human host response to NYVAC...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.80.2.985-998.2006

    authors: Guerra S,López-Fernández LA,Pascual-Montano A,Nájera JL,Zaballos A,Esteban M

    更新日期:2006-01-01 00:00:00

  • Characterization of envelope glycoprotein mutants for human T-cell leukemia virus type 1 infectivity and immortalization.

    abstract::The human T-cell leukemia virus type 1 (HTLV-1) envelope protein is required for virus spread. This study further characterizes the role of the envelope protein in HTLV-1 immortalization. Viruses with single amino acid substitutions within the SU protein at residue 75, 81, 95, 101, 105, or 195 or with a C-terminal cyt...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.75.19.9553-9559.2001

    authors: Tsukahara T,Wielgosz MM,Ratner L

    更新日期:2001-10-01 00:00:00

  • cis-Acting signals involved in termination of vesicular stomatitis virus mRNA synthesis include the conserved AUAC and the U7 signal for polyadenylation.

    abstract::We investigated the cis-acting sequences involved in termination of vesicular stomatis virus mRNA synthesis by using bicistronic genomic analogs. All of the cis-acting signals necessary for termination reside within the first 13 nucleotides of the 23-nucleotide conserved gene junction. This 13-nucleotide termination s...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.71.11.8718-8725.1997

    authors: Barr JN,Whelan SP,Wertz GW

    更新日期:1997-11-01 00:00:00

  • Neuroadapted yellow fever virus 17D: determinants in the envelope protein govern neuroinvasiveness for SCID mice.

    abstract::A molecular clone of mouse-neuroadapted yellow fever 17D virus (SPYF-MN) was used to identify critical determinants of viral neuroinvasiveness in a SCID mouse model. Virus derived from this clone differs from nonneuroinvasive YF5.2iv virus at 29 nucleotide positions, encoding 13 predicted amino acid substitutions and ...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/jvi.77.22.12232-12242.2003

    authors: Nickells M,Chambers TJ

    更新日期:2003-11-01 00:00:00

  • Structure of adeno-associated virus type 4.

    abstract::Adeno-associated virus (AAV) is a member of the Parvoviridae, belonging to the Dependovirus genus. Currently, several distinct isolates of AAV are in development for use in human gene therapy applications due to their ability to transduce different target cells. The need to manipulate AAV capsids for specific tissue d...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.79.8.5047-5058.2005

    authors: Padron E,Bowman V,Kaludov N,Govindasamy L,Levy H,Nick P,McKenna R,Muzyczka N,Chiorini JA,Baker TS,Agbandje-McKenna M

    更新日期:2005-04-01 00:00:00

  • Brome mosaic virus helicase- and polymerase-like proteins colocalize on the endoplasmic reticulum at sites of viral RNA synthesis.

    abstract::The helicase-like 1a and polymerase-like 2a proteins of brome mosaic virus (BMV) are required for viral RNA replication in vivo, are present in membrane-bound viral RNA polymerase extracts, and share conservation with the many other members of the alphavirus-like superfamily. To better understand BMV RNA replication a...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.70.12.8908-8916.1996

    authors: Restrepo-Hartwig MA,Ahlquist P

    更新日期:1996-12-01 00:00:00

  • The Toll-like receptor 7 (TLR7) agonist, imiquimod, and the TLR9 agonist, CpG ODN, induce antiviral cytokines and chemokines but do not prevent vaginal transmission of simian immunodeficiency virus when applied intravaginally to rhesus macaques.

    abstract::The initial host response to viral infection occurs after Toll-like receptors (TLRs) on dendritic cells (DC) are stimulated by viral nucleic acids (double-stranded RNA, single-stranded RNA) and alpha interferon (IFN-alpha) and IFN-beta are produced. We hypothesized that pharmacologic induction of innate antiviral resp...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.79.22.14355-14370.2005

    authors: Wang Y,Abel K,Lantz K,Krieg AM,McChesney MB,Miller CJ

    更新日期:2005-11-01 00:00:00