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

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

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
JournalPLoS Pathogens
Volume3
Issue number11
DOIs
StatePublished - Nov 2007

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Endogenous Retroviruses
HIV Infections
HIV-1
T-Lymphocytes
Peptides
Human Genome
Viral Load
Immunity
Enzyme-Linked Immunospot Assay
AIDS Vaccines

ASJC Scopus subject areas

  • Microbiology
  • Parasitology
  • Virology
  • Immunology
  • Genetics
  • Molecular Biology

Cite this

Garrison, K. E., Jones, R. B., Meiklejohn, D. A., Anwar, N., Ndhlovu, L. C., Chapman, J. M., ... Nixon, D. F. (2007). T cell responses to human endogenous retroviruses in HIV-1 infection. PLoS Pathogens, 3(11). https://doi.org/10.1371/journal.ppat.0030165

T cell responses to human endogenous retroviruses in HIV-1 infection. / Garrison, Keith E.; Jones, R. Brad; Meiklejohn, Duncan A.; Anwar, Naveed; Ndhlovu, Lishomwa C.; Chapman, Joan M.; Erickson, Ann L.; Agrawal, Ashish; Spotts, Gerald; Hecht, Frederick M.; Rakoff-Nahoum, Seth; Lenz, Jack; Ostrowski, Mario A.; Nixon, Douglas F.

In: PLoS Pathogens, Vol. 3, No. 11, 11.2007.

Research output: Contribution to journalArticle

Garrison, KE, Jones, RB, Meiklejohn, DA, Anwar, N, Ndhlovu, LC, Chapman, JM, Erickson, AL, Agrawal, A, Spotts, G, Hecht, FM, Rakoff-Nahoum, S, Lenz, J, Ostrowski, MA & Nixon, DF 2007, 'T cell responses to human endogenous retroviruses in HIV-1 infection.', PLoS Pathogens, vol. 3, no. 11. https://doi.org/10.1371/journal.ppat.0030165
Garrison KE, Jones RB, Meiklejohn DA, Anwar N, Ndhlovu LC, Chapman JM et al. T cell responses to human endogenous retroviruses in HIV-1 infection. PLoS Pathogens. 2007 Nov;3(11). https://doi.org/10.1371/journal.ppat.0030165
Garrison, Keith E. ; Jones, R. Brad ; Meiklejohn, Duncan A. ; Anwar, Naveed ; Ndhlovu, Lishomwa C. ; Chapman, Joan M. ; Erickson, Ann L. ; Agrawal, Ashish ; Spotts, Gerald ; Hecht, Frederick M. ; Rakoff-Nahoum, Seth ; Lenz, Jack ; Ostrowski, Mario A. ; Nixon, Douglas F. / T cell responses to human endogenous retroviruses in HIV-1 infection. In: PLoS Pathogens. 2007 ; Vol. 3, No. 11.
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