Abstract:
:The nonstructural protein (NSs) of severe fever with thrombocytopenia syndrome phlebovirus (SFTSV) sequesters TANK-binding kinase 1 (TBK1) into NSs-induced cytoplasmic structures to inhibit the phosphorylation and nuclear translocation of interferon (IFN) regulatory factor 3 (IRF3) and subsequent interferon beta (IFN-β) production. Although the C-terminal region of SFTSV NSs (NSs66-249) has been linked to the formation of NSs-induced cytoplasmic structures and inhibition of host IFN-β responses, the role of the N-terminal region in antagonizing host antiviral responses remains to be defined. Here, we demonstrate that two conserved amino acids at positions 21 and 23 in the SFTSV and heartland virus (HRTV) NSs are essential for suppression of IRF3 phosphorylation and IFN-β mRNA expression following infection with SFTSV or recombinant influenza virus lacking the NS1 gene. Surprisingly, formation of SFTSV/HRTV NSs-induced cytoplasmic structures is not essential for inhibition of host antiviral responses. Rather, an association between SFTSV/HRTV NSs and TBK1 is required for suppression of mitochondrial antiviral signaling protein (MAVS)-mediated activation of IFN-β promoter activity. Although SFTSV NSs did not prevent the ubiquitination of TBK1, it associates with TBK1 through its N-terminal kinase domain (residues 1 to 307) to block the autophosphorylation of TBK1. Furthermore, we found that both wild-type NSs and the 21/23A mutant (NSs in which residues at positions 21 and 23 were replaced with alanine) of SFTSV suppressed NLRP3 inflammasome-dependent interleukin-1β (IL-1β) secretion, suggesting that the importance of these residues is restricted to TBK1-dependent IFN signaling. Together, our findings strongly implicate the two conserved amino acids at positions 21 and 23 of SFTSV/HRTV NSs in the inhibition of host interferon responses.IMPORTANCE Recognition of viruses by host innate immune systems plays a critical role not only in providing resistance to viral infection but also in the initiation of antigen-specific adaptive immune responses against viruses. Severe fever with thrombocytopenia syndrome (SFTS) is a newly emerging infectious disease caused by the SFTS phlebovirus (SFTSV), a highly pathogenic tick-borne phlebovirus. The 294-amino-acid nonstructural protein (NSs) of SFTSV associates with TANK-binding kinase 1 (TBK1), a key regulator of host innate antiviral immunity, to inhibit interferon beta (IFN-β) production and enhance viral replication. Here, we demonstrate that two conserved amino acids at positions 21 and 23 in the NSs of SFTSV and heartland virus, another tick-borne phlebovirus, are essential for association with TBK1 and suppression of IFN-β production. Our results provide important insight into the molecular mechanisms by which SFTSV NSs helps to counteract host antiviral strategies.
journal_name
J Viroljournal_title
Journal of virologyauthors
Moriyama M,Igarashi M,Koshiba T,Irie T,Takada A,Ichinohe Tdoi
10.1128/JVI.00706-18subject
Has Abstractpub_date
2018-09-12 00:00:00issue
19eissn
0022-538Xissn
1098-5514pii
JVI.00706-18journal_volume
92pub_type
杂志文章abstract::Equine rhinitis A virus (ERAV) has recently been classified as an aphthovirus, a genus otherwise comprised of the different serotypes of Foot-and-mouth disease virus (FMDV). FMDV initiates translation via a type II internal ribosomal entry site (IRES) and utilizes two in-frame AUG codons to produce the leader proteina...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.74.24.11708-11716.2000
更新日期:2000-12-01 00:00:00
abstract::The protein kinase inhibitor H7 blocks influenza virus replication, inhibits production of the matrix protein (M1), and leads to a retention of the viral ribonucleoproteins (vRNPs) in the nucleus at late times of infection (K. Martin and A. Helenius, Cell 67:117-130, 1991). We show here that production of assembled vR...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.74.4.1781-1786.2000
更新日期:2000-02-01 00:00:00
abstract::The barley stripe mosaic virus (BSMV) beta(b) gene product is the major viral nonstructural protein synthesized during early stages of the infection cycle and is required for systemic movement of the virus. To examine the biochemical properties of beta(b), a histidine tag was engineered at the amino terminus and the p...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.71.2.1538-1546.1997
更新日期:1997-02-01 00:00:00
abstract::A specific endoribonucleolytic activity was detected when detergent-lysed vesicular stomatitis of Sendai virus was incubated with the precursor to Escherichia coli tRNA Tyr. The cleavage products produced and the characteristics of the reaction were similar to those previously reported for human KB cell RNase NU. Like...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.25.1.274-284.1978
更新日期:1978-01-01 00:00:00
abstract::Interferon-induced transmembrane protein 3 (IFITM3) is a cellular factor that reduces HIV-1 infectivity by an incompletely understood mechanism. We show here that viruses differing only in the envelope glycoprotein (Env) expressed on their surface have different sensitivities to IFITM3. Measurements of the sensitivity...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01994-20
更新日期:2020-12-09 00:00:00
abstract::A sequence of polyadenylic acid, homogeneous in composition but heterogeneous in length, was isolated from complete pancreatic RNase digests of both middle and bottom RNAs of cowpea mosaic virus. The polyadenylic acid was 3'-terminal and occurred once per molecule. A fragment consisting of the polyadenylic acid and ap...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.26.2.243-248.1978
更新日期:1978-05-01 00:00:00
abstract::Subcutaneous injection of FK506 (10 mg/kg of body weight) completely blocked the clonal expansion of staphylococcal enterotoxin A (SEA)-reactive T cells in healthy (control) mice after SEA injection but did not disturb it in mice with murine AIDS (MAIDS) caused by infection with LP-BM5 murine leukemia virus. MAIDS mic...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.71.1.746-749.1997
更新日期:1997-01-01 00:00:00
abstract::The murine monoclonal antibody (MAb) 5A8, which is reactive with domain 2 of CD4, blocks human immunodeficiency virus type 1 (HIV-1) infection and syncytium formation of CD4+ cells (L. C. Burkly, D. Olson, R. Shapiro, G. Winkler, J. J. Rosa, D. W. Thomas, C. Williams, and P. Chisholm, J. Immunol., in press). Here we s...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.66.8.4784-4793.1992
更新日期:1992-08-01 00:00:00
abstract::Wild-type bacteriophage phie and IS (interference-sensitive) mutants of the related phage SP82G did not productively infect strains of Bacillus subtilis that were lysogenic for temperate phage SPO2. In these abortive infections, the sensitive phages adsorbed to and penetrated the nonpermissive host, phage-directed mac...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.18.3.839-847.1976
更新日期:1976-06-01 00:00:00
abstract::HLA-B*52:01 is strongly associated with protection against HIV disease progression. However, the mechanisms of HLA-B*52:01-mediated immune control have not been well studied. We here describe a cohort with a majority of HIV C-clade-infected individuals from Delhi, India, where HLA-B*52:01 is highly prevalent (phenotyp...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02025-19
更新日期:2020-06-16 00:00:00
abstract::Defective reovirions lacking the largest (L-1) of the normal 10 genomic segments grow only in association with helper reovirus. Because of the similarity in properties of defective and infectious virions, separation of the two populations by physical methods has been unseccessful. Controlled digestion of purified viru...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.15.4.954-963.1975
更新日期:1975-04-01 00:00:00
abstract::We evaluated the ability of human coronaviruses to infect primary cultures of human neural cells. Double immunofluorescence with antibodies to virus and cell markers showed infection of fetal astrocytes and of adult microglia and astrocytes by strain OC43. RNA amplification revealed infection of fetal astrocytes, adul...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.71.1.800-806.1997
更新日期:1997-01-01 00:00:00
abstract::Epstein-Barr virus (EBV) establishes a persistent latent infection in B lymphocytes and is associated with the development of numerous human tumors. Epstein-Barr nuclear antigen 3C (EBNA 3C) is essential for B-cell immortalization, has potent cell cycle deregulation capabilities, and functions as a regulator of both v...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.07161-11
更新日期:2012-05-01 00:00:00
abstract::T7 early mRNA's are generated from a high-molecular-weight precursor RNA by site-specific RNase III cleavage. When T7 DNA is transcribed in vitro by Escherichia coli RNA polymerase, the transcript is a large, single-piece RNA equivalent to the in vivo precursor RNA. The T7 RNA synthesized in vitro can be translated as...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.18.3.1155-1159.1976
更新日期:1976-06-01 00:00:00
abstract::Epstein-Barr virus is associated with several human malignancies including Burkitt's lymphoma, nasopharyngeal carcinoma, and Hodgkin's disease (HD). To examine the effect of Epstein-Barr virus nuclear antigen 1 (EBNA-1) in the pathogenesis of HD, we transfected the gene into the HD cell line L428. EBNA-1 expression wa...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.73.2.1630-1636.1999
更新日期:1999-02-01 00:00:00
abstract::The wild-type strain of vesicular stomatitis virus (VSV) contains in its complete virion (VSV-1, B particles) a minus strand RNA. The principle defective particle of the wild-type strain (VSV-111, T particles) contains a shorter minus strand, homologous to part of the VSV-1 genome. Neither virion contains any detectab...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.11.6.915-925.1973
更新日期:1973-06-01 00:00:00
abstract::Recent studies of varicella-zoster virus (VZV) DNA sequence variation, involving large numbers of globally distributed clinical isolates, suggest that this virus has diverged into at least three distinct genotypes designated European (E), Japanese (J), and mosaic (M). In the present study, we determined and analyzed t...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00835-06
更新日期:2006-10-01 00:00:00
abstract::A phage, designated CP-51, that carries out generalized transduction in Bacillus cereus 569 was isolated from soil. All auxotrophic mutants tested, those requiring tryptophan, histidine, leucine, isoleucine, methionine, or phenylalanine, were transduced to prototrophy. The phage was extremely unstable when stored at 2...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.2.7.657-662.1968
更新日期:1968-07-01 00:00:00
abstract:UNLABELLED:Bluetongue is one of the major infectious diseases of ruminants and is caused by bluetongue virus (BTV), an arbovirus existing in nature in at least 26 distinct serotypes. Here, we describe the development of a vaccine platform for BTV. The advent of synthetic biology approaches and the development of revers...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02183-14
更新日期:2014-11-01 00:00:00
abstract::Sendai virus (SV) and human parainfluenza virus type 1 (hPIV1) have genomes consisting of nonsegmented negative-sense RNA in which the six genes are separated by well-conserved intergenic (IG) sequences and transcriptional start (S) and end signals. In hPIV1-infected cells, transcriptional termination at the M-F gene ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.16.8244-8251.2002
更新日期:2002-08-01 00:00:00
abstract::Murine gammaherpesvirus 68 (MHV-68) glycoprotein B (gB) was identified in purified virions by immunoblotting, immunoprecipitation, and immunoelectron microscopy. It was synthesized as a 120-kDa precursor in infected cells and cleaved into 65-kDa and 55-kDa disulfide-linked subunits close to the time of virion release....
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.78.23.13370-13375.2004
更新日期:2004-12-01 00:00:00
abstract::The sensitivity of highly purified human fibroblast interferon and partially purified human leukocyte interferon to several proteolytic and glycolytic enzymes was determined with respect to antiviral activity, isoelectric point, molecular weight, and thermal stability. Leucine aminopeptidase altered the distribution o...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.35.2.390-399.1980
更新日期:1980-08-01 00:00:00
abstract::The nr allele at the mouse Fv1 restriction locus governs resistance to B-tropic and some N-tropic murine leukemia viruses (MLVs). Sequence analysis and site-specific mutagenesis of N-tropic MLVs identified a single amino acid difference responsible for this restriction that is distinct from the site that governs N or ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.74.11.5385-5387.2000
更新日期:2000-06-01 00:00:00
abstract::Herein we demonstrate that chronic simian immunodeficiency virus (SIV) infection induces significant upregulation of the gut-homing marker alpha4beta7 on macaque NK cells, coupled with downregulation of the lymph node-trafficking marker, CCR7. Interestingly, in naïve animals, alpha4beta7 expression was associated with...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01126-10
更新日期:2010-09-01 00:00:00
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
更新日期:2011-03-01 00:00:00
abstract::Inhibitors of hemagglutination by type A2 influenza virus and a recently isolated strain of type B influenza virus were separated by sucrose density gradient centrifugation and agarose gel filtration from horse serum. Using selected reagents, it was demonstrated that the active substituent on the horse serum inhibitor...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.3.5.477-483.1969
更新日期:1969-05-01 00:00:00
abstract::In Epstein-Barr virus (EBV)-carrying nonproducer Raji cells, the induction of the viral replicative cycle by chemical treatment is limited to only the early stage and viral DNA synthesis is totally inhibited. We previously showed the absence of two messenger RNAs that are encoded by the BamHI-A fragment of the EBV gen...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.11.7309-7314.1995
更新日期:1995-11-01 00:00:00
abstract::The human cytidine deaminase Apobec3F (h-A3F), a protein related to the previously recognized antiviral factor Apobec3G (h-A3G), has antiviral activity against human immunodeficiency virus type 1 (HIV-1) that is suppressed by the viral protein Vif. The mechanism of HIV-1 Vif-mediated suppression of h-A3F is not fully ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.79.15.9579-9587.2005
更新日期:2005-08-01 00:00:00
abstract::Apoptosis of infected cells is critically involved in antiviral defense. Apoptosis, however, may also support the release and spread of viruses. Although the elimination of infected hepatocytes is required to combat hepatitis B virus (HBV) infection, it is still unknown which consequences hepatocyte apoptosis has for ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00653-10
更新日期:2010-11-01 00:00:00
abstract::Understanding the mechanism(s) of action of the hepatitis B virus (HBV)-encoded protein HBx is fundamental to elucidating the underlying mechanisms of chronic liver disease and hepatocellular carcinoma caused by HBV infection. In our continued attempts to identify cellular targets of HBx, we have previously reported t...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.74.6.2840-2846.2000
更新日期:2000-03-01 00:00:00