16th International AIDS Conference Toronto, Canada - August 13 - 18, 2006

T CELL RESPONSES TO HUMAN ENDOGENOUS RETROVIRUSES IN PRIMARY HIV INFECTION: A NOVEL VACCINE STRATEGY?

Int Conf AIDS. 2006 Aug 13-18;16 Abstract No. WeAa0404

Garrison K.¹, Jones R.B.², Meiklejohn D.A.¹, Agrawal A.¹, Anwar N.², Spotts G.³, Hecht F.M.³, Rakoff-Nahoum S.⁴, Lenz J.⁵, Ostrowski M.A.², Nixon D.F.^1
1 Gladstone Institute, University of California San Francisco, Gladstone Institute of Virology and Immunology, San Francisco, United States, ² University of Toronto, Department of Immunology, Toronto, Canada, ³ University of California San Francisco, Positive Health Program, San Francisco, United States, ⁴ Yale University, New Haven, United States, ⁵ Albert Einstein College of Medicine, New York, United States

BACKGROUND: Human endogenous Retrovirus (HERV) sequences make up roughly 8% of the human genome. Some HERV insertions have distinct blocks of similarity to HIV, which could lead to deletions of reactive T cells during development. We hypothesized that regions of HERV-HIV similarity would be poorly immunogenic.

METHODS: BLAST searches were used to identify regions of similarity. An alignment of the HIV and HERV-K reverse transcriptase protein sequences overlayed with the Los Alamos HIV epitope map was used to correlate regions of high HERV-HIV similarity and epitope-poor regions in HIV. HERV-derived peptides with varying levels of similarity to HIV epitopes were used to enumerate interferon-g producing T cells. HERV and HIV-specific responses were measured in 25 individuals with primary HIV infection and 5 HIV-uninfected volunteers. Expression levels of a HERV-derived transcript were determined with qPCR from plasma of HIV-infected individuals.

RESULTS: Regions of HIV-HERV similarity did not correspond to epitope-poor regions of HIV. Responses to the most HIV-similar HERV peptides occurred early in infection, whereas strong T cell responses directed at HIV-dissimilar HERV regions were only evident later in infection. In addition, we detected HERV-K transcripts in plasma of HIV-infected patients which correlated with HIV viral load.

CONCLUSIONS: The presence of T cell responses to HERV peptides indicates a lack of immune tolerance to HERVs in HIV-infected individuals. HIV infection leads to increased expression of HERVs. Induction of a HERV-specific response in HIV infection results in a two-pronged attack on the virus. HERV-specific T cells can attack HIV-infected cells through cross-recognition of HIV epitopes. Presentation of HERV epitopes by HIV-infected cells makes them the target of the HERV-specific response. Studies are underway to determine if these responses modulate HIV disease progression. The limited variability of genome-encoded HERV epitopes makes them an effective surrogate target for an HIV vaccine.

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2006-08-13
WeAa0404

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