| HERV-K-specific T cells eliminate diverse HIV-1/2 and SIV primary isolates. | |
| | |
MedLine Citation:
|
PMID: 23143309 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
The genetic diversity of HIV-1 represents a major challenge in vaccine development. In this study, we establish a rationale for eliminating HIV-1-infected cells by targeting cellular immune responses against stable human endogenous retroviral (HERV) antigens. HERV DNA sequences in the human genome represent the remnants of ancient infectious retroviruses. We show that the infection of CD4+ T cells with HIV-1 resulted in transcription of the HML-2 lineage of HERV type K [HERV-K(HML-2)] and the expression of Gag and Env proteins. HERV-K(HML-2)-specific CD8+ T cells obtained from HIV-1-infected human subjects responded to HIV-1-infected cells in a Vif-dependent manner in vitro. Consistent with the proposed mode of action, a HERV-K(HML-2)-specific CD8+ T cell clone exhibited comprehensive elimination of cells infected with a panel of globally diverse HIV-1, HIV-2, and SIV isolates in vitro. We identified a second T cell response that exhibited cross-reactivity between homologous HIV-1-Pol and HERV-K(HML-2)-Pol determinants, raising the possibility that homology between HIV-1 and HERVs plays a role in shaping, and perhaps enhancing, the T cell response to HIV-1. This justifies the consideration of HERV-K(HML-2)-specific and cross-reactive T cell responses in the natural control of HIV-1 infection and for exploring HERV-K(HML-2)-targeted HIV-1 vaccines and immunotherapeutics. |
| | |
Authors:
|
R Brad Jones; Keith E Garrison; Shariq Mujib; Vesna Mihajlovic; Nasra Aidarus; Diana V Hunter; Eric Martin; Vivek M John; Wei Zhan; Nabil F Faruk; Gabor Gyenes; Neil C Sheppard; Ingrid M Priumboom-Brees; David A Goodwin; Lianchun Chen; Melanie Rieger; Sophie Muscat-King; Peter T Loudon; Cole Stanley; Sara J Holditch; Jessica C Wong; Kiera Clayton; Erick Duan; Haihan Song; Yang Xu; Devi SenGupta; Ravi Tandon; Jonah B Sacha; Mark A Brockman; Erika Benko; Colin Kovacs; Douglas F Nixon; Mario A Ostrowski |
Related Documents
:
|
23233639 - Are you sure this is waldenstrom macroglobulinemia? 22996319 - Alloantigen specific regulatory t cells prevent experimental chronic graft-versus-host ... 17587739 - Cardiac cell therapy and arrhythmias. 23100519 - Identification of an mhc class i ligand for the single member of a killer cell lectin-l... 23671799 - No factor left behind: generation of transgene-free induced pluripotent stem cells. 19492979 - Lost in translation: what is limiting cardiomyoplasty and can tissue engineering help? 23233639 - Are you sure this is waldenstrom macroglobulinemia? 7828409 - Peripheral blood lymphocyte subsets in multiple myeloma and monoclonal gammopathy of un... 11473729 - Expression of drug resistance genes in vp-16 and mamsa-selected human carcinoma cells. |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2012-11-12 |
Journal Detail:
|
Title: The Journal of clinical investigation Volume: 122 ISSN: 1558-8238 ISO Abbreviation: J. Clin. Invest. Publication Date: 2012 Dec |
Date Detail:
|
Created Date: 2012-12-03 Completed Date: 2013-02-04 Revised Date: 2013-02-20 |
Medline Journal Info:
|
Nlm Unique ID: 7802877 Medline TA: J Clin Invest Country: United States |
Other Details:
|
Languages: eng Pagination: 4473-89 Citation Subset: AIM; IM |
Affiliation:
|
Department of Immunology, University of Toronto, and Li Ka Shing Knowledge Institute, St. Michael’s Hospital, Toronto, Ontario, Canada. bjones.ut@gmail.com |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Amino Acid Sequence Animals Antigens, Viral / genetics, immunology, metabolism CD4-Positive T-Lymphocytes / immunology, virology* Cells, Cultured Endogenous Retroviruses / immunology, metabolism, physiology* Gene Expression Regulation, Viral Gene Products, gag / genetics, immunology, metabolism HIV Infections / immunology, virology HIV-1 / immunology, isolation & purification, physiology* HIV-2 / immunology, isolation & purification, physiology* Host-Pathogen Interactions Humans Immunity, Cellular* Molecular Sequence Data Simian immunodeficiency virus / immunology, isolation & purification, physiology* Transcriptional Activation Viral Envelope Proteins / genetics, immunology, metabolism Virus Integration Virus Internalization vif Gene Products, Human Immunodeficiency Virus / physiology |
| Grant Support | |
ID/Acronym/Agency:
|
AI076059/AI/NIAID NIH HHS; AI084113/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Antigens, Viral; 0/Gene Products, gag; 0/Viral Envelope Proteins; 0/vif Gene Products, Human Immunodeficiency Virus; 0/vif protein, Human immunodeficiency virus 1 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Kras(G12D) and Nkx2-1 haploinsufficiency induce mucinous adenocarcinoma of the lung.
Next Document: Persistent Truncus Arteiosus With Double Aortic Arch and Mitral Stenosis.