Abstract:
UNLABELLED:The interferon (IFN)-mediated antiviral response is a central aspect of host defense; however, viruses have evolved multiple strategies to counteract IFN-mediated responses in order to successfully infect the host. Herpes simplex virus 1 (HSV-1), a typical human-restricted DNA virus, is capable of counteracting host immune responses via several distinct viral proteins, thus establishing a lifelong latent infection. In this study, we demonstrate that the VP24 protein, a serine protease of HSV-1 essential for the formation and maturation of capsids, is a novel antagonist of the beta interferon (IFN-β) pathway. Here, VP24 was shown for the first time to dampen interferon stimulatory DNA (ISD)-triggered IFN-β production and inhibit IFN-β promoter activation induced by cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING) and by STING, respectively. Further study demonstrated that ectopic expression of VP24 selectively blocked IFN regulatory factor 3 (IRF3) but not NF-κB promoter activation. In addition, VP24 was demonstrated to downregulate ISD-induced phosphorylation and dimerization of IRF3 during HSV-1 infection with a VP24 stable knockdown human foreskin fibroblast cell line. The underlying molecular mechanism is that VP24 abrogates the interaction between TANK-binding kinase 1 (TBK1) and IRF3, hence impairing IRF3 activation. These results illustrate that VP24 is able to block the production of IFN-β by inhibiting IRF3 activation, which may represent a critical adaptation to enable viral effective replication within the host. IMPORTANCE:This study demonstrated that HSV-1 protein VP24 could inhibit IFN-β production and promoter activation triggered by ISD, cGAS and STING and by STING, respectively. VP24 selectively blocked IRF3 promoter activation and ISD-induced phosphorylation and dimerization of IRF3 without affecting the NF-κB promoter activation during viral infection. VP24 also inhibited IRF3 activation by impeding the interaction between TBK1 and IRF3 during viral infection. This study provides new insights into the immune evasion mediated by HSV-1 and identifies VP24 as a crucial effector for HSV-1 to evade the host DNA-sensing signal pathway.
journal_name
J Viroljournal_title
Journal of virologyauthors
Zhang D,Su C,Zheng Cdoi
10.1128/JVI.00186-16subject
Has Abstractpub_date
2016-05-27 00:00:00pages
5824-5829issue
12eissn
0022-538Xissn
1098-5514pii
JVI.00186-16journal_volume
90pub_type
杂志文章abstract::The gD, gB, and gH/gL glycoprotein quartet constitutes the basic apparatus for herpes simplex virus (HSV) entry into the cell and fusion. gD serves as a receptor binding glycoprotein and trigger of fusion. The conserved gB and gH/gL execute fusion. Central to understanding HSV entry/fusion has become the dissection of...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01287-09
更新日期:2009-10-01 00:00:00
abstract::Human T-cell lymphotropic virus type 1 (HTLV-1) enhances the growth of T lymphocytes, allowing the generation of T-lymphocyte cell lines. This report describes a limiting-dilution assay system which uses low input numbers of HTLV-1-producing cells for generation of T-lymphocyte cultures. The HTLV-1 transformants gener...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.10.6297-6303.1995
更新日期:1995-10-01 00:00:00
abstract::A number of naturally occurring hepatitis B virus mutants that cannot synthesize the virus precore protein have been identified. Such mutants have been associated with more severe forms of hepatitis, including fulminant hepatitis. The most common mutation observed is a substitution of G to A in the distal precore gene...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.66.9.5682-5684.1992
更新日期:1992-09-01 00:00:00
abstract::The Graffi murine leukemia virus (MuLV) is a retroviral mixture that induces predominantly myeloid leukemia in several inbred strains of mice. To analyze the viral component responsible for the myeloid leukemogenesis, we cloned several proviruses from a Graffi MuLV-infected cell line. Several infectious molecular clon...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.67.8.4722-4731.1993
更新日期:1993-08-01 00:00:00
abstract::Evidence is presented that, in frog virus 3-infected BHK cells, inhibition of ribonucleic acid (RNA) synthesis is paralleled by a decreased activity of host cell RNA polymerase II, while the template ability of host cell nuclei and chromatin is unaffected. ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.9.4.698-700.1972
更新日期:1972-04-01 00:00:00
abstract::Previous studies with simian virus 40-transformed mouse 3T3 cells which are temperature sensitive for the expression of the transformed phenotype (ts SV3T3 cells) have shown that T-antigen expression and viral DNA transcription are under cell cycle control. Using these ts SV3T3 cells, we studied the expression of the ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.30.3.711-719.1979
更新日期:1979-06-01 00:00:00
abstract::To clarify the role of core protein phosphorylation in pregenomic-RNA encapsidation of human and duck hepatitis B viruses (HBV and DHBV, respectively), we have examined the phosphorylation states of different forms of intracellular HBV core protein and the phenotypic effects of mutations in the phosphorylation sites o...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.74.10.4721-4728.2000
更新日期:2000-05-01 00:00:00
abstract::The parvovirus minute virus of mice (MVM) packages predominantly negative-sense single strands, while its close relative LuIII encapsidates strands of both polarities with equal efficiency. Using genomic chimeras and mutagenesis, we show that the ability to package positive strands maps not, as originally postulated, ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.79.4.2287-2300.2005
更新日期:2005-02-01 00:00:00
abstract::The human cytomegalovirus UL47 open reading frame encodes a 110-kDa protein that is a component of the virion tegument. We have constructed a cytomegalovirus mutant, ADsubUL47, in which the central portion of the UL47 open reading frame has been replaced by two marker genes. The mutant replicated to titers 100-fold lo...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.3.1043-1050.2002
更新日期:2002-02-01 00:00:00
abstract::Lipoxins are host anti-inflammatory molecules that play a vital role in restoring tissue homeostasis. The efficacy of lipoxins and their analog epilipoxins in treating inflammation and its associated diseases has been well documented. Kaposi's sarcoma (KS) and primary effusion lymphoma (PEL) are two well-known inflamm...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01491-16
更新日期:2016-11-28 00:00:00
abstract::During viral infection, inflammation and recovery are tightly controlled by competing proinflammatory and regulatory immune pathways. Respiratory syncytial virus (RSV) is the leading global cause of infantile bronchiolitis, which is associated with recurrent wheeze and asthma diagnosis in later life. Th2-driven diseas...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01295-13
更新日期:2013-10-01 00:00:00
abstract::The complete genome sequences of the human coronavirus OC43 (HCoV-OC43) laboratory strain from the American Type Culture Collection (ATCC), and a HCoV-OC43 clinical isolate, designated Paris, were obtained. Both genomes are 30,713 nucleotides long, excluding the poly(A) tail, and only differ by 6 nucleotides. These si...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.78.16.8824-8834.2004
更新日期:2004-08-01 00:00:00
abstract::Recent studies suggest the existence of cancer stem cells (CSC) and cancer progenitor cells (CPC), although strict definitions of neither CSC nor CPC have been developed. We have produced evidence that the principal oncoprotein of Epstein-Barr virus (EBV), latent membrane protein 1 (LMP1), which is associated with hum...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00188-11
更新日期:2011-11-01 00:00:00
abstract::The antiviral effects of nitric oxide (NO) on Japanese encephalitis virus (JEV), a member of the family Flaviviridae, were investigated in this study. In vitro, inhibition of replication of JEV in gamma interferon-activated RAW 264.7 murine macrophages was correlated to cellular NO production. When cocultured with inf...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.71.7.5227-5235.1997
更新日期:1997-07-01 00:00:00
abstract::Human immunodeficiency virus type 1 uses ribosomal frameshifting for translation of the Gag-Pol polyprotein. Frameshift activities are thought to be tightly regulated. Analysis of gag p1 sequences from 270 plasma virions identified in 64% of the samples the occurrence of polymorphism that could lead to changes in ther...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.15.7868-7873.2002
更新日期:2002-08-01 00:00:00
abstract::Epstein-Barr virus (EBV) transforms B lymphocytes through the expression of the latent viral proteins EBNA and latent membrane protein (LMP). Recently, it has become apparent that microRNAs (miRNAs) also contribute to EBV's oncogenic properties; recombinant EBVs that lack the BHRF1 miRNA cluster display a reduced abil...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.05100-11
更新日期:2011-10-01 00:00:00
abstract::The genome of infectious bursal disease virus consists of two segments of double-stranded RNA of 2.5 X 10(6) and 2.2 X 10(6) molecular weight. Polyacrylamide gel electrophoresis of purified virus resolved four structural polypeptides: VP-1 (90,000), VP-2 (41,000), VP-3 (35,000), and VP-4 (28,000). Peptide map comparis...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.32.3.1047-1050.1979
更新日期:1979-12-01 00:00:00
abstract::Polydnaviridae is a unique family of DNA viruses that are symbiotically associated with parasitoid wasps. Upon oviposition, wasps inject these viruses into their hosts, where they cause several physiological alterations, including suppression of the cellular immune response. Here we report that expression of the glc1....
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.79.3.1861-1870.2005
更新日期:2005-02-01 00:00:00
abstract::The murine polyomavirus (Py) enters mouse fibroblasts and kidney epithelial cells via an endocytic pathway that is caveola-independent (as well as clathrin-independent). In contrast, uptake of simian virus 40 into the same cells is dependent on caveola. Following the initial uptake of Py, both microtubules and microfi...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.77.4.2615-2622.2003
更新日期:2003-02-01 00:00:00
abstract::The group A rotaviruses are composed of at least seven serotypes. Serotype specificity is defined mainly by an outer capsid protein, VP7. In contrast, the other surface protein, VP3 (775 amino acids), appears to be associated with both serotype-specific and heterotypic immunity. To identify the cross-reactive and sero...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.62.7.2421-2426.1988
更新日期:1988-07-01 00:00:00
abstract::Retroviral capsid assembly can occur by either of two distinct morphogenic processes: in type C viruses, the capsid assembles and buds at the plasma membrane, while in type B and D viruses, the capsid assembles within the cytoplasm and is then transported to the plasma membrane for budding. We have previously reported...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.73.7.5431-5437.1999
更新日期:1999-07-01 00:00:00
abstract::Besides its role in viral assembly, the vesicular stomatitis virus (VSV) matrix (M) protein causes cytopathic effects such as cell rounding (D. Blondel, G. G. Harmison, and M. Schubert, J. Virol. 64:1716-1725, 1990). DNA cotransfection assays demonstrated that VSV M protein was able to inhibit the transcription of a r...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.6.3529-3537.1995
更新日期:1995-06-01 00:00:00
abstract::Previous reports (H. Delius and J. B. Clements, J. Gen. Virol. 33:125-134, 1976; G. S. Hayward, R. J. Jacob, S. C. Wadsworth, and B. Roizman, Proc. Natl. Acad. Sci. U.S.A. 72:4243-4247, 1975; B. Roizman, G. S. Hayward, R. Jacob, S. W. Wadsworth, and R. W. Honess, Excerpta Med. Int. Congr. Ser. 2:188-198, 1974) have sh...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.29.2.448-457.1979
更新日期:1979-02-01 00:00:00
abstract::Coxsackievirus B3 (CVB3) is an enterovirus in the family Picornaviridae that is significant to human health, being associated with myocarditis, aseptic meningitis, and pancreatitis, among other conditions. In addition to humans, Sichuan snub-nosed monkeys can be infected and killed by CVB3. Here, we report the first c...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02365-12
更新日期:2012-12-01 00:00:00
abstract::Recently, recombinant baculoviruses have been used to show that expression of six herpes simplex virus type 1 genes results in the formation of capsid-like particles. We have applied cryoelectron microscopy and three-dimensional image reconstruction to establish their structural authenticity to a resolution of approxi...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.11.7362-7366.1995
更新日期:1995-11-01 00:00:00
abstract::Herpes simplex virus (HSV) glycoprotein D (gD) is modified with mannose 6-phosphate (M6P) and binds to M6P receptors (MPRs). MPRs are involved in the well-characterized pathway by which lysosomal enzymes are directed to lysosomes via a network of endosomal membranes. Based on the impaired ability of HSV to form plaque...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.72.4.3330-3339.1998
更新日期:1998-04-01 00:00:00
abstract::The UL16 protein of herpes simplex virus is capsid associated and was previously identified as a binding partner of the membrane-associated UL11 tegument protein (J. S. Loomis, R. J. Courtney, and J. W. Wills, J. Virol. 77:11417-11424, 2003). In those studies, a less-prominent, approximately 65-kDa binding partner of ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02015-09
更新日期:2010-03-01 00:00:00
abstract::Ribosomes are observed intimately associated with nucleocapsids of vesicular, stomatitis virus, especially those that line structures that are either cytoplasmic vesicles or invaginations of the plasma membrane. ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.16.2.447-452.1975
更新日期:1975-08-01 00:00:00
abstract::Recent evidence suggests that the type II feline coronavirus (FCoV) strains 79-1146 and 79-1683 have arisen from a homologous RNA recombination event between FCoV type I and canine coronavirus (CCV). In both cases, the template switch apparently took place between the S and M genes, giving rise to recombinant viruses ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.72.5.4508-4514.1998
更新日期:1998-05-01 00:00:00
abstract::A panel of 28 insertion mutants of the human immunodeficiency virus type 1 (HIV-1) Gag precursor (Pr55Gag) was constructed by linker-insertion mutagenesis and expressed in recombinant baculovirus-infected insect cells. One set of 14 mutants carried the normal N-myristylation signal; the other set constituted their non...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.68.1.111-122.1994
更新日期:1994-01-01 00:00:00