Reciprocal Cross Heterologous Immunity between Human Endogenous Retrovirus and HIV-1 Provides a Novel HIV-1 Vaccine Strategy
Keith Garrison*1, B Jones2, D Meiklejohn1, L Ndhlovu1, A Agrawal1, F Hecht1, S Rakoff-Nahoum3, J Lenz4, M Ostrowski2, and D Nixon1
1Univ of California, San Francisco, US; 2Univ of Toronto, Canada; 3Yale Univ, New Haven, CT, US; and 4Albert Einstein Coll of Med, Bronx, NY, US
Background: Human endogenous retrovirus (HERV) sequences
make up 8% of the human genome. Under normal circumstances HERV are
functionally defective or controlled by host factors. In HIV-1-infected
patients, intracellular defense mechanisms are compromised. We hypothesized
that HIV-1 infection could alter controls on HERV activity, and expression of
HERV antigens could stimulate a T-cell response cross-reactive with HIV-1.
Methods: We examined plasma from 16 HIV-1+
and 4 HIV-1– subjects for HERV transcripts using real time polymerase chain reaction (qRT-PCR). We then tested HERV peptides for T-cell immunogenicity in 31 subjects with primary HIV-1 infection
and 4 low-risk HIV-1– controls using the interferon-gamma
ELISpot. Phenotyping of
responding cells was determined using flow cytometry.
Results: We detected significantly greater levels of
HERV-K transcripts in the plasma of HIV-1-infected subjects compared to HIV-1–
controls (Mann-Whitney, p = 0.0160).
All HIV-1+ subjects had T-cell reactivity to HERV peptides in the ELISpot assay. Phenotyping of
HERV-specific T cells showed both CD8+ and CD4+ T-cell
Conclusions: HIV-1 infection leads to HERV expression and
stimulation of HERV-specific T cells. As a novel vaccine strategy against
HIV-1, elicitation of HERV-specific responses would lead to T cells that recognize
HIV-1-infected cells by 2 mechanisms: recognition of HERV expression in HIV-1-infected
cells and through cross-reactivity against HIV-1.