Abstract:
:The DNA sensing pathway triggers innate immune responses against DNA virus infection, and NF-κB signaling plays a critical role in establishing innate immunity. We report here that the herpes simplex virus 1 (HSV-1) ubiquitin-specific protease (UL36USP), which is a deubiquitinase (DUB), antagonizes NF-κB activation, depending on its DUB activity. In this study, ectopically expressed UL36USP blocked promoter activation of beta interferon (IFN-β) and NF-κB induced by cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING). UL36USP restricted NF-κB activation mediated by overexpression of STING, TANK-binding kinase 1, IκB kinase α (IKKα), and IKKβ, but not p65. UL36USP was also shown to inhibit IFN-stimulatory DNA-induced IFN-β and NF-κB activation under conditions of HSV-1 infection. Furthermore, UL36USP was demonstrated to deubiquitinate IκBα and restrict its degradation and, finally, abrogate NF-κB activation. More importantly, the recombinant HSV-1 lacking UL36USP DUB activity, denoted as C40A mutant HSV-1, failed to cleave polyubiquitin chains on IκBα. For the first time, UL36USP was shown to dampen NF-κB activation in the DNA sensing signal pathway to evade host antiviral innate immunity.IMPORTANCE It has been reported that double-stranded-DNA-mediated NF-κB activation is critical for host antiviral responses. Viruses have established various strategies to evade the innate immune system. The N terminus of the HSV-1 UL36 gene-encoded protein contains the DUB domain and is conserved across all herpesviruses. This study demonstrates that UL36USP abrogates NF-κB activation by cleaving polyubiquitin chains from IκBα and therefore restricts proteasome-dependent degradation of IκBα and that DUB activity is indispensable for this process. This study expands our understanding of the mechanisms utilized by HSV-1 to evade the host antiviral innate immune defense induced by NF-κB signaling.
journal_name
J Viroljournal_title
Journal of virologyauthors
Ye R,Su C,Xu H,Zheng Cdoi
10.1128/JVI.02417-16subject
Has Abstractpub_date
2017-02-14 00:00:00issue
5eissn
0022-538Xissn
1098-5514pii
JVI.02417-16journal_volume
91pub_type
杂志文章abstract:UNLABELLED:The emergence of Middle East respiratory syndrome-coronavirus (MERS-CoV) in the Middle East since 2012 has caused more than 900 human infections with ∼40% mortality to date. Animal models are needed for studying pathogenesis and for development of preventive and therapeutic agents against MERS-CoV infection....
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doi:10.1128/JVI.03427-14
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.6.3038-3044.2002
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abstract::Hpt-13 is a Chinese hamster cell line deficient in hypoxanthine phosphoribosyltransferase (EC 2.4.2.8) and sensitive to a medium containing 10(-4) M hypoxanthine, 5.5 X 10(-6) M aminopterin, and 10(-4) M thymidine. In this cell line there is a high incidence of cells resistant to this selective medium after an incubat...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.38.1.184-190.1981
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abstract::The human airway epithelium (HAE) represents the entry port of many human respiratory viruses, including human coronaviruses (HCoVs). Nowadays, four HCoVs, HCoV-229E, HCoV-OC43, HCoV-HKU1, and HCoV-NL63, are known to be circulating worldwide, causing upper and lower respiratory tract infections in nonhospitalized and ...
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pub_type: 杂志文章
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pub_type: 杂志文章
doi:10.1128/JVI.25.1.395-407.1978
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abstract::Hepatitis A virus (HAV) has previously been reported to bind to human red blood cells through interaction with glycophorin A. Residue K221 of VP1 and the surrounding VP3 residues are involved in such an interaction. This capsid region is specifically recognized by the monoclonal antibody H7C27. A monoclonal antibody-r...
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pub_type: 杂志文章
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pub_type: 杂志文章
doi:10.1128/jvi.74.22.10563-10570.2000
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abstract::Baculoviruses, although they infect insects in nature, can transduce a wide variety of mammalian cells and are therefore promising gene therapy vectors. However, baculovirus transduction into many mammalian cells is very inefficient, and the limiting stages and factors remain unknown. An important finding is that a sh...
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pub_type: 杂志文章
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01404-16
更新日期:2016-10-14 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00462-13
更新日期:2013-09-01 00:00:00
abstract::Immunosuppressed patients are at risk for developing Epstein-Barr Virus (EBV)-positive lymphomas that express the major EBV oncoprotein, LMP1. Although increasing evidence suggests that a small number of lytically infected cells may promote EBV-positive lymphomas, the impact of enhanced lytic gene expression on the ab...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00770-12
更新日期:2012-08-01 00:00:00
abstract::Human T-cell lymphotropic virus type 1 (HTLV-1) is transmitted through a viral synapse and enters target cells via interaction with the glucose transporter GLUT1. Here, we show that Neuropilin-1 (NRP1), the receptor for semaphorin-3A and VEGF-A165 and a member of the immune synapse, is also a physical and functional p...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02719-05
更新日期:2006-07-01 00:00:00
abstract::The entry of enveloped viruses into cells is normally mediated by fusion between viral and cellular membranes, in which the fusion peptide plays a crucial role. The fusion peptides of group II nucleopolyhedrovirus (NPV) F proteins are quite conserved, with a hydrophobic region located at the N terminal of the F(1) fra...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00368-08
更新日期:2008-08-01 00:00:00
abstract::Hepatitis A virus (HAV) is an enterically transmitted virus that replicates predominantly in hepatocytes within the liver before excretion via bile through feces. Hepatocytes are polarized epithelial cells, and it has been assumed that the virus load in bile results from direct export of HAV via the apical domain of p...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00219-08
更新日期:2008-09-01 00:00:00
abstract::Processing of the hepatitis C virus polyprotein is accomplished by a series of cotranslational and posttranslational cleavages mediated by host cell signalases and two virally encoded proteinases. Of these the NS3 proteinase is essential for processing at the NS3/4A, NS4A/4B, NS4B/5A, and NS5A/5B junctions. Processing...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.1.198-205.1995
更新日期:1995-01-01 00:00:00
abstract::Human cytomegalovirus (HCMV) infection has been shown to activate the mTORC1 signaling pathway. However, the phosphorylation of mTORC1 targets is differentially sensitive to the mTORC1 inhibitor rapamycin, and the drug inhibits HCMV replication to a modest extent. Using Torin1, a newly developed inhibitor that targets...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02733-09
更新日期:2010-05-01 00:00:00
abstract::Hepatitis A virus (HAV), an atypical member of the Picornaviridae, grows poorly in cell culture. To define determinants of HAV growth, we introduced a blasticidin (Bsd) resistance gene into the virus genome and selected variants that grew at high concentrations of Bsd. The mutants grew fast and had increased rates of ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01470-09
更新日期:2010-08-01 00:00:00
abstract::Amphiphilic fatty acid derivatives having a 14- to 20-carbon cis-unsaturated alkyl chain were found to be potent inhibitors of the entry process of the lipid-containing bacteriophage PR4. ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.29.1.413-416.1979
更新日期:1979-01-01 00:00:00
abstract::Nucleocapsids were isolated from purified enveloped nucleocapsids of Plodia interpunctella granulosis virus by treatment with Nonidet P-40. When analyzed on sodium dodecyl sulfate-polyacrylamide gels, the nucleocapsids consisted of eight polypeptides. One of these, a major component with a molecular weight of 12,500 (...
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pub_type: 杂志文章
doi:10.1128/JVI.33.2.866-876.1980
更新日期:1980-02-01 00:00:00
abstract::Autonomous parvoviruses are thought to uniquely encapsidate single-stranded DNA of minus polarity. In contrast, the defective adeno-associated viruses separately encapsidate equal amounts of plus and minus DNA strands. We reexamined the uniqueness of minus strand encapsidation for the autonomous parvoviruses. Although...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.49.2.319-324.1984
更新日期:1984-02-01 00:00:00
abstract::Alternative splicing of adeno-associated virus type 2 (AAV2) P19-generated pre-mRNAs generates the small Rep proteins Rep52 and Rep40, which differ in their carboxyl termini. Both proteins are required for optimal packaging of AAV2 genomes. AAV5 Rep-encoding P19-generated transcripts are primarily polyadenylated withi...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01961-09
更新日期:2010-01-01 00:00:00
abstract::Transmission of human immunodeficiency virus type 1 (HIV-1) occurs primarily via the mucosal route, suggesting that HIV-1 vaccines may need to elicit mucosal immune responses. Here, we investigated the immunogenicity and relative efficacy of systemic immunization with two human ALVAC-HIV-1 recombinant vaccines express...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.80.8.3732-3742.2006
更新日期:2006-04-01 00:00:00
abstract::We have characterized by T1 fingerprint analysis several defective interfering (DI) double-stranded RNAs of the simple yeast virus ScV. A common sequence of about 0.5 to 0.6 kilobase pairs, including both 3' termini of the parental RNA, was present in each DI RNA. Several DI RNAs had novel T1 oligonucleotides not pres...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.32.2.692-696.1979
更新日期:1979-11-01 00:00:00
abstract::Varicella-zoster virus (VZV) DNA was prepared from nucleocapsids and from enveloped virions of a laboratory strain (Ellen) and directly from the vesicle fluids of patients with zoster infections. VZV Ellen nucleocapsid DNA was cleaved with 11 different restriction endonucleases and electrophoresed in agarose gels. The...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.40.2.516-525.1981
更新日期:1981-11-01 00:00:00
abstract::Natural killer (NK) cells are components of the innate immunity and are key players in the defense against virus-infected and malignant cells. NK cells are particularly important in the innate defense against herpesviruses, including alphaherpesviruses. Aggravated and life-threatening alphaherpesvirus-induced disease ...
journal_title:Journal of virology
pub_type: 杂志文章
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更新日期:2019-03-21 00:00:00
abstract::Tryptic digests of the internal proteins p30, p15, p12, and p10 of mouse xenotropic, ecotropic, and amphotropic type C viruses were subjected to cation-exchange chromatography. Analysis of these maps revealed that the p30 proteins from representative isolates of all three viral subgroups were distinguishable. The p15 ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.29.1.102-113.1979
更新日期:1979-01-01 00:00:00
abstract::In 2002, severe acute respiratory syndrome (SARS)-coronavirus (CoV) appeared as a novel human virus with high similarity to bat coronaviruses. However, while SARS-CoV uses the human angiotensin-converting enzyme 2 (ACE2) receptor for cellular entry, no coronavirus isolated from bats appears to use ACE2. Here we show t...
journal_title:Journal of virology
pub_type: 杂志文章
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更新日期:2012-06-01 00:00:00
abstract::The sole immediate-early (IE) gene of equine herpesvirus 1 encodes a 1,487-amino-acid (aa) regulatory phosphoprotein that independently activates expression of early viral genes. Coimmunoprecipitation assays demonstrated that the IE protein physically interacts with the general transcription factor TFIIB. Using a vari...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.75.21.10219-10230.2001
更新日期:2001-11-01 00:00:00