T cell responses to human endogenous retroviruses in HIV-1 infection.

Human endogenous retroviruses (HERVs) are remnants of ancient infectious agents that have integrated into the human genome. Under normal circumstances, HERVs are functionally defective or controlled by host factors. In HIV-1-infected individuals, intracellular defense mechanisms are compromised. We...

Full description

Bibliographic Details
Main Authors: Keith E Garrison, R Brad Jones, Duncan A Meiklejohn, Naveed Anwar, Lishomwa C Ndhlovu, Joan M Chapman, Ann L Erickson, Ashish Agrawal, Gerald Spotts, Frederick M Hecht, Seth Rakoff-Nahoum, Jack Lenz, Mario A Ostrowski, Douglas F Nixon
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2007-11-01
Series:PLoS Pathogens
Online Access:https://doi.org/10.1371/journal.ppat.0030165
id doaj-a8303acd1f5b468b9a449226feeb4925
record_format Article
spelling doaj-a8303acd1f5b468b9a449226feeb49252021-04-21T17:20:38ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742007-11-01311e16510.1371/journal.ppat.0030165T cell responses to human endogenous retroviruses in HIV-1 infection.Keith E GarrisonR Brad JonesDuncan A MeiklejohnNaveed AnwarLishomwa C NdhlovuJoan M ChapmanAnn L EricksonAshish AgrawalGerald SpottsFrederick M HechtSeth Rakoff-NahoumJack LenzMario A OstrowskiDouglas F NixonHuman endogenous retroviruses (HERVs) are remnants of ancient infectious agents that have integrated into the human genome. Under normal circumstances, HERVs are functionally defective or controlled by host factors. In HIV-1-infected individuals, intracellular defense mechanisms are compromised. We hypothesized that HIV-1 infection would remove or alter controls on HERV activity. Expression of HERV could potentially stimulate a T cell response to HERV antigens, and in regions of HIV-1/HERV similarity, these T cells could be cross-reactive. We determined that the levels of HERV production in HIV-1-positive individuals exceed those of HIV-1-negative controls. To investigate the impact of HERV activity on specific immunity, we examined T cell responses to HERV peptides in 29 HIV-1-positive and 13 HIV-1-negative study participants. We report T cell responses to peptides derived from regions of HERV detected by ELISPOT analysis in the HIV-1-positive study participants. We show an inverse correlation between anti-HERV T cell responses and HIV-1 plasma viral load. In HIV-1-positive individuals, we demonstrate that HERV-specific T cells are capable of killing cells presenting their cognate peptide. These data indicate that HIV-1 infection leads to HERV expression and stimulation of a HERV-specific CD8+ T cell response. HERV-specific CD8+ T cells have characteristics consistent with an important role in the response to HIV-1 infection: a phenotype similar to that of T cells responding to an effectively controlled virus (cytomegalovirus), an inverse correlation with HIV-1 plasma viral load, and the ability to lyse cells presenting their target peptide. These characteristics suggest that elicitation of anti-HERV-specific immune responses is a novel approach to immunotherapeutic vaccination. As endogenous retroviral sequences are fixed in the human genome, they provide a stable target, and HERV-specific T cells could recognize a cell infected by any HIV-1 viral variant. HERV-specific immunity is an important new avenue for investigation in HIV-1 pathogenesis and vaccine design.https://doi.org/10.1371/journal.ppat.0030165
collection DOAJ
language English
format Article
sources DOAJ
author Keith E Garrison
R Brad Jones
Duncan A Meiklejohn
Naveed Anwar
Lishomwa C Ndhlovu
Joan M Chapman
Ann L Erickson
Ashish Agrawal
Gerald Spotts
Frederick M Hecht
Seth Rakoff-Nahoum
Jack Lenz
Mario A Ostrowski
Douglas F Nixon
spellingShingle Keith E Garrison
R Brad Jones
Duncan A Meiklejohn
Naveed Anwar
Lishomwa C Ndhlovu
Joan M Chapman
Ann L Erickson
Ashish Agrawal
Gerald Spotts
Frederick M Hecht
Seth Rakoff-Nahoum
Jack Lenz
Mario A Ostrowski
Douglas F Nixon
T cell responses to human endogenous retroviruses in HIV-1 infection.
PLoS Pathogens
author_facet Keith E Garrison
R Brad Jones
Duncan A Meiklejohn
Naveed Anwar
Lishomwa C Ndhlovu
Joan M Chapman
Ann L Erickson
Ashish Agrawal
Gerald Spotts
Frederick M Hecht
Seth Rakoff-Nahoum
Jack Lenz
Mario A Ostrowski
Douglas F Nixon
author_sort Keith E Garrison
title T cell responses to human endogenous retroviruses in HIV-1 infection.
title_short T cell responses to human endogenous retroviruses in HIV-1 infection.
title_full T cell responses to human endogenous retroviruses in HIV-1 infection.
title_fullStr T cell responses to human endogenous retroviruses in HIV-1 infection.
title_full_unstemmed T cell responses to human endogenous retroviruses in HIV-1 infection.
title_sort t cell responses to human endogenous retroviruses in hiv-1 infection.
publisher Public Library of Science (PLoS)
series PLoS Pathogens
issn 1553-7366
1553-7374
publishDate 2007-11-01
description Human endogenous retroviruses (HERVs) are remnants of ancient infectious agents that have integrated into the human genome. Under normal circumstances, HERVs are functionally defective or controlled by host factors. In HIV-1-infected individuals, intracellular defense mechanisms are compromised. We hypothesized that HIV-1 infection would remove or alter controls on HERV activity. Expression of HERV could potentially stimulate a T cell response to HERV antigens, and in regions of HIV-1/HERV similarity, these T cells could be cross-reactive. We determined that the levels of HERV production in HIV-1-positive individuals exceed those of HIV-1-negative controls. To investigate the impact of HERV activity on specific immunity, we examined T cell responses to HERV peptides in 29 HIV-1-positive and 13 HIV-1-negative study participants. We report T cell responses to peptides derived from regions of HERV detected by ELISPOT analysis in the HIV-1-positive study participants. We show an inverse correlation between anti-HERV T cell responses and HIV-1 plasma viral load. In HIV-1-positive individuals, we demonstrate that HERV-specific T cells are capable of killing cells presenting their cognate peptide. These data indicate that HIV-1 infection leads to HERV expression and stimulation of a HERV-specific CD8+ T cell response. HERV-specific CD8+ T cells have characteristics consistent with an important role in the response to HIV-1 infection: a phenotype similar to that of T cells responding to an effectively controlled virus (cytomegalovirus), an inverse correlation with HIV-1 plasma viral load, and the ability to lyse cells presenting their target peptide. These characteristics suggest that elicitation of anti-HERV-specific immune responses is a novel approach to immunotherapeutic vaccination. As endogenous retroviral sequences are fixed in the human genome, they provide a stable target, and HERV-specific T cells could recognize a cell infected by any HIV-1 viral variant. HERV-specific immunity is an important new avenue for investigation in HIV-1 pathogenesis and vaccine design.
url https://doi.org/10.1371/journal.ppat.0030165
work_keys_str_mv AT keithegarrison tcellresponsestohumanendogenousretrovirusesinhiv1infection
AT rbradjones tcellresponsestohumanendogenousretrovirusesinhiv1infection
AT duncanameiklejohn tcellresponsestohumanendogenousretrovirusesinhiv1infection
AT naveedanwar tcellresponsestohumanendogenousretrovirusesinhiv1infection
AT lishomwacndhlovu tcellresponsestohumanendogenousretrovirusesinhiv1infection
AT joanmchapman tcellresponsestohumanendogenousretrovirusesinhiv1infection
AT annlerickson tcellresponsestohumanendogenousretrovirusesinhiv1infection
AT ashishagrawal tcellresponsestohumanendogenousretrovirusesinhiv1infection
AT geraldspotts tcellresponsestohumanendogenousretrovirusesinhiv1infection
AT frederickmhecht tcellresponsestohumanendogenousretrovirusesinhiv1infection
AT sethrakoffnahoum tcellresponsestohumanendogenousretrovirusesinhiv1infection
AT jacklenz tcellresponsestohumanendogenousretrovirusesinhiv1infection
AT marioaostrowski tcellresponsestohumanendogenousretrovirusesinhiv1infection
AT douglasfnixon tcellresponsestohumanendogenousretrovirusesinhiv1infection
_version_ 1714666187361615872