Abstract:
:Major histocompatibility complex E (MHC-E) is a highly conserved nonclassical MHC-Ib molecule that tightly binds peptides derived from leader sequences of classical MHC-Ia molecules for presentation to natural killer cells. However, MHC-E also binds diverse foreign and neoplastic self-peptide antigens for presentation to CD8+ T cells. Although the determinants of MHC-E-restricted T cell priming remain unknown, these cells are induced in humans infected with pathogens containing genes that inhibit the transporter associated with antigen processing (TAP). Indeed, mice vaccinated with TAP-inhibited autologous dendritic cells develop T cells restricted by the murine MHC-E homologue, Qa-1b. Here, we tested whether rhesus macaques (RM) vaccinated with viral constructs expressing a TAP inhibitor would develop insert-specific MHC-E-restricted CD8+ T cells. We generated viral constructs coexpressing SIVmac239 Gag in addition to one of three TAP inhibitors: herpes simplex virus 2 ICP47, bovine herpes virus 1 UL49.5, or rhesus cytomegalovirus Rh185. Each TAP inhibitor reduced surface expression of MHC-Ia molecules but did not reduce surface MHC-E expression. In agreement with modulation of surface MHC-Ia levels, TAP inhibition diminished presentation of MHC-Ia-restricted CD8+ T cell epitopes without impacting presentation of peptide antigen bound by MHC-E. Vaccination of macaques with vectors dually expressing SIVmac239 Gag with ICP47, UL49.5, or Rh185 generated Gag-specific CD8+ T cells classically restricted by MHC-Ia but not MHC-E. These data demonstrate that, in contrast to results in mice, TAP inhibition alone is insufficient for priming of MHC-E-restricted T cell responses in primates and suggest that additional unknown mechanisms govern the induction of CD8+ T cells recognizing MHC-E-bound antigen.IMPORTANCE Due to the near monomorphic nature of MHC-E in the human population and inability of many pathogens to inhibit MHC-E-mediated peptide presentation, MHC-E-restricted T cells have become an attractive vaccine target. However, little is known concerning how these cells are induced. Understanding the underlying mechanisms that induce these T cells would provide a powerful new vaccine strategy to an array of neoplasms and viral and bacterial pathogens. Recent studies have indicated a link between TAP inhibition and induction of MHC-E-restricted T cells. The significance of our research is in demonstrating that TAP inhibition alone does not prime MHC-E-restricted T cell generation and suggests that other, currently unknown mechanisms regulate their induction.
journal_name
J Viroljournal_title
Journal of virologyauthors
Abdulhaqq SA,Wu H,Schell JB,Hammond KB,Reed JS,Legasse AW,Axthelm MK,Park BS,Asokan A,Früh K,Hansen SG,Picker LJ,Sacha JBdoi
10.1128/JVI.00592-19subject
Has Abstractpub_date
2019-09-12 00:00:00issue
19eissn
0022-538Xissn
1098-5514pii
JVI.00592-19journal_volume
93pub_type
杂志文章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::The hepadnavirus reverse transcriptase is a multifunction enzyme. In addition to its role in DNA synthesis, the polymerase is required for RNA packaging and also functions as the primer for minus-strand DNA synthesis. Previously, we demonstrated that the protein-priming activity of the polymerase requires a viral RNA ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.68.12.8437-8442.1994
更新日期:1994-12-01 00:00:00
abstract::Extracts made from human respiratory syncytial virus (RSV)-infected Hep-2 cells synthesized mRNAs encoded by all known viral genes. In contrast, RSV ribonucleoproteins purified from infected cells failed to transcribe in vitro; transcription was restored by addition of a cytoplasmic extract of uninfected Hep-2 cells, ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.66.11.6813-6818.1992
更新日期:1992-11-01 00:00:00
abstract::Chick embryo cells became more sensitive to the action of interferon the longer they remained in culture. This phenomenon was found even before confluency had been reached. The relative insensitivity of newly seeded cells was not due to a loss of receptors. Cells synthesizing deoxyribonucleic acid (DNA) at a high rate...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.4.1.7-11.1969
更新日期:1969-07-01 00:00:00
abstract::Our previous studies have argued persuasively that in murine sarcoma virus ts110 (MuSVts110) the gag and mos genes are fused out of frame due to a approximately 1.5-kilobase (kb) deletion of wild-type murine sarcoma virus 349 (MuSV-349) viral information. As a consequence of this deletion, infected cells grown at 39 d...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.53.2.624-633.1985
更新日期:1985-02-01 00:00:00
abstract::The presence of porcine endogenous retroviruses presents a potential risk of transmission of infectious diseases (xenozoonosis) if tissues and organs from genetically modified pigs are to be used in xenotransplantation. Here, we report that intracellular expression of a llama single-domain antibody against p15, the ma...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.77.22.12132-12139.2003
更新日期:2003-11-01 00:00:00
abstract:UNLABELLED:Human cytomegalovirus (hCMV) infection is characterized by a vast expansion of resting effector-type virus-specific T cells in the circulation. In mice, interleukin-7 receptor α (IL-7Rα)-expressing cells contain the precursors for long-lived antigen-experienced CD8(+) T cells, but it is unclear if similar me...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02003-14
更新日期:2015-01-01 00:00:00
abstract::We constructed a DNA fragment map of low-passage Towne strain cytomegalovirus by analyzing cross-blot hybridization and hybridizations of isolated recombinant clones. The abundant late transcripts were located on this map by hybridization of labeled total RNA of virus-infected cells to blotted DNA fragments. The most ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.52.1.129-135.1984
更新日期:1984-10-01 00:00:00
abstract::A cDNA fragment coding for poliovirus capsid polypeptide VP1 was inserted into a simian virus 40 (SV40) genome in the place of the SV40 VP1 gene and fused in phase to the 3' end of the VP2-VP3 genes. Simian cells were infected with the resulting hybrid virus in the presence of an early SV40 mutant used as a helper. In...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.61.12.3862-3869.1987
更新日期:1987-12-01 00:00:00
abstract::The human cytomegalovirus UL4 gene encodes a 48-kDa glycoprotein, expression of which is repressed at the translational level by a short upstream open reading frame (uORF2) within the UL4 transcript leader. Mutation of the uORF2 initiation codon in the viral genome eliminates ribosomal stalling at the uORF2 terminatio...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.75.15.7188-7192.2001
更新日期:2001-08-01 00:00:00
abstract::The herpes simplex virus type 1 (HSV-1) tegument is the least understood component of the virion, and the mechanism of tegument assembly and incorporation into virions during viral egress has not yet been elucidated. In the present study, the addition of tegument proteins (VP13/14, VP16, VP22, and US9) and envelope gl...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.19.9934-9951.2002
更新日期:2002-10-01 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::The small envelope protein (E) plays a role of central importance in the assembly of coronaviruses. This was initially established by studies demonstrating that cellular expression of only E protein and the membrane protein (M) was necessary and sufficient for the generation and release of virus-like particles. To inv...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01577-06
更新日期:2007-03-01 00:00:00
abstract::The major obstacle to human immunodeficiency type 1 virus (HIV-1) eradication is a reservoir of latently infected cells that persists despite long-term antiretroviral therapy (ART) and is maintained through cellular proliferation. Long-lived memory CD4+ T cells with high self-renewal capacity, such as central memory (...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01094-19
更新日期:2019-12-12 00:00:00
abstract::White spot syndrome virus (WSSV) is a crustacean-infecting, double-stranded DNA virus and is the most serious viral pathogen in the global shrimp industry. WSSV is the sole recognized member of the family Nimaviridae, and the lack of genomic data on other nimaviruses has obscured the evolutionary history of WSSV. Here...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01144-18
更新日期:2019-01-17 00:00:00
abstract:UNLABELLED:Arthritogenic alphaviruses such as Ross River virus (RRV) and chikungunya virus (CHIKV) cause large-scale epidemics of severe musculoskeletal disease and have been progressively expanding their global distribution. Since its introduction in July 2014, CHIKV now circulates in the United States. The hallmark o...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00224-15
更新日期:2015-08-01 00:00:00
abstract::The development of resistance to host defense mechanisms such as tumor necrosis factor (TNF)- and Fas-mediated apoptosis of transformed or virus-infected cells may be a critical component in the development of disease. To find genes that protect cells from apoptosis, we used an expression cloning strategy and identifi...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.71.10.7509-7517.1997
更新日期:1997-10-01 00:00:00
abstract::Human immunodeficiency virus type 1 (HIV-1) is frequently attenuated after long-term culture in vitro. The attenuation process probably involves mutations of functions required for replication and pathogenicity in vivo. Analysis of attenuated HIV-1 for replication and pathogenicity in vivo will help to define these fu...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.75.8.3916-3924.2001
更新日期:2001-04-01 00:00:00
abstract::The humoral immune response of cats that were naturally infected with the feline leukemia virus (FeLV) was examined after antigenic stimulation with the synthetic antigen poly(L-Tyr, L-Glu)-poly(DL-Ala)-poly(L-Lys). The primary humoral antibody response in FeLV-infected cats was both delayed and greatly reduced, compa...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.60.2.669-673.1986
更新日期:1986-11-01 00:00:00
abstract::Murine norovirus (MNV), a prevalent pathogen of laboratory mice, shares many characteristics with human noroviruses. Previous results indicated that passage of MNV1 in the macrophage cell line RAW 264.7 results in attenuation in STAT1-deficient mice (C. E. Wobus, S. M. Karst, L. B. Thackray, K. O. Chang, S. V. Sosnovt...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00237-08
更新日期:2008-08-01 00:00:00
abstract::When residues 17 and 18 in nef of simian immunodeficiency virus strain SIVmac239 were changed from RQ to YE, the resultant virus was able to replicate in peripheral blood mononuclear cell cultures without prior lymphocyte activation and without the addition of exogenous interleukin-2, caused extensive lymphocyte activ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.70.6.4157-4161.1996
更新日期:1996-06-01 00:00:00
abstract::A well-characterized mechanism by which anti-HLA class I monoclonal antibodies (MAb) inhibit human immunodeficiency virus type 1 (HIV-1) propagation in in vitro cell cultures is the neutralization of the virus through interactions with HLA molecules associated with the virion envelope. Yet, the possibility that anothe...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.70.8.5213-5220.1996
更新日期:1996-08-01 00:00:00
abstract::Viruses are both inducers and targets of posttranscriptional gene silencing (PTGS), a natural defense mechanism in plants. Here we report molecular evidence of the ability of single-stranded DNA (ssDNA) viruses to induce PTGS in infected plants irrespective of the severity of or recovery from the symptoms. Our results...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.78.14.7465-7477.2004
更新日期:2004-07-01 00:00:00
abstract::Griffithsin, which binds N-linked glycans on gp120 to prevent HIV entry, has the most potent HIV-1 inhibitory activity described for any antiviral lectin and is being developed for topical preexposure prophylaxis. The current studies were designed to further assess its potential by exploring its activity against herpe...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00012-13
更新日期:2013-06-01 00:00:00
abstract::Phosphorylation of the murine mammary tumor virus (MuMTV) structural proteins was studied in an MuMTV-infected epithelial cell line derived from a BALB/cf C3H mouse mammary tumor. Immunoprecipitation of 32P-labeled cell extracts with monospecific anti-p27 serum revealed that phosphorylation occurred at the stage of th...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.30.1.241-247.1979
更新日期:1979-04-01 00:00:00
abstract::Three polyadenylated RNAs, 9, 7.3, and 3.5 kilobases long, of a human endogenous retrovirus, ERV3, are abundant in human placental chorion, representing about 0.03 to 0.05% of the total mRNA. We characterized the structure of these mRNAs by Northern blot and S1 nuclease mapping analyses. We found that all three RNAs w...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.61.7.2182-2191.1987
更新日期:1987-07-01 00:00:00
abstract::Active proteinase 3C of hepatitis A virus (HAV) was expressed in bacteria either as a mature enzyme or as a protein fused to the entire polymerase 3D or to a part of it, and their identities were shown by immunoblot analysis. Intermolecular cleavage activity was demonstrated by incubating in vitro-translated and radio...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.66.11.6794-6796.1992
更新日期:1992-11-01 00:00:00
abstract:UNLABELLED:The lipid kinase phosphatidylinositol 4-kinase III alpha (PI4KIIIα) is an endoplasmic reticulum (ER)-resident enzyme that synthesizes phosphatidylinositol 4-phosphate (PI4P). PI4KIIIα is an essential host factor for hepatitis C virus (HCV) replication. Interaction with HCV nonstructural protein 5A (NS5A) lea...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01063-14
更新日期:2014-09-01 00:00:00
abstract::Here we show that the adenovirus early region 4 (E4) open reading frame 4 (ORF4) protein autoregulates its own transcription by inhibiting adenovirus E1A-induced activation of E4 transcription both in transient transfection experiments and during lytic virus growth. The inhibitory activity of E4-ORF4 was selective for...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.70.6.3844-3851.1996
更新日期:1996-06-01 00:00:00
abstract::Varicella-zoster virus (VZV) encodes within its unique long region a gene product with protein kinase motifs. In a previous study, we demonstrated that immunoprecipitated VZV open reading frame (ORF) 47 protein was associated with a functional protein kinase activity, on the basis of its ability to both autophosphoryl...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.68.3.1350-1359.1994
更新日期:1994-03-01 00:00:00