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Dodging HIV Variability by Targeting HERVs

November 14, 2012

In prior posts I've written about research from the laboratories of Mario Ostrowski and Doug Nixon looking at the effect of HIV infection on human endogenous retrovirus (HERV) protein expression. This work, led by Brad Jones and Keith Garrison, has shown that the liberating effects of the HIV Vif protein can cause normally inactive HERV genetic sequences to produce proteins in cells infected by HIV. These proteins can then be processed and presented as antigens and, as a consequence, HERV-specific CD8 T-cell responses are detectable in some individuals with HIV. However, up until now there has been no direct evidence that HERV-specific CD8 T-cell responses can actually recognize and kill HIV-infected CD4 T cells. A paper just published in the Journal of Clinical Investigation addresses this information gap, demonstrating that CD8 T cells specific for a HERV-K(HML-2) epitope are able to recognize and kill CD4 T cells infected with an array of HIV-1, HIV-2, and SIV isolates (albeit with varying levels of effectiveness depending on the specific isolate).

Based on their findings, the researchers suggest that induction of HERV-K(HML-2)-specific CD8 T-cell responses using vaccines may offer a way to target HIV-infected cells without having to deal with the problem of HIV's genetic variability. One serious concern with this approach is that, if HERV-K(HML-2) proteins are ever expressed by healthy cells, autoimmunity could ensue. But so far, the authors note, "expression of HERV-K(HML-2)-Gag and -Env protein has not been convincingly demonstrated in any healthy adult human tissue, despite extensive screening." Additional studies are now planned to assess whether targeting HERV-K(HML-2) might have potential in the context of both therapeutic and preventive HIV vaccine strategies.

Richard Jefferys is the coordinator of the Michael Palm HIV Basic Science, Vaccines & Prevention Project Weblog at the Treatment Action Group (TAG). The original blog post may be viewed here.

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