Document Detail


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
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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:  2013-12-04    
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    
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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; R01 AI076059/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

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