Two interesting presentations on the first day of CROI related to human endogenous retroviruses (HERVs). HERVs are essentially fossil remnants of retroviruses that humans encountered many millennia ago; they can no longer replicate but rather have incorporated into human DNA and now make up a surprising 8% of our genome. Some rare HERV sequences (e.g. HERV-K) exist as full length proviruses but fragments known as human endogenous retrotransposable elements (HERE) are more common. Human cells have restriction factors like the recently discovered APOBEC proteins which suppress retroviral activity and these factors are believed to keep endogenous retroviral sequences dormant. However, it is known that HIV has evolved mechanisms (such as the viral protein Vif) which disable host restriction factors. This led researcher Brad Jones from the University of Toronto to wonder if perhaps HIV infection of CD4 cells would awaken endogenous retroviral sequences and allow them to become active.
When Jones looked at HIV-infected primary CD4 T cell lines in vitro, this is exactly what he found. These cells accumulated increasing numbers of genomic copies of the HEREs that Jones tested for (AluSX, LINE-1 and segments of HERV-K), but uninfected CD4 cells did not. To take a preliminary look at whether such events occur in vivo, Jones searched databases of HIV sequences and found a primary HIV isolate into which a HERE (LINE-1) had become inserted, strongly suggesting that HIV and LINE-1 can be active in the same cell.
Further supporting Jones's reasoning, Keith Garrison from UCSF presented a poster (#457) showing that people with HIV have higher levels of HERV-K genetic material in their blood compared to uninfected controls. Furthermore, T cell responses to HERV-K protein fragments (peptides) could be detected in individuals with primary HIV infection but not in uninfected controls. There was even a weak but statistically significant inverse correlation between HERV-K-specific T cell responses and HIV viral load (r2=0.11, p=0.03).
These findings may suggest novel strategies for HIV vaccines and immunotherapies. HIV's notorious ability to mutate makes it a difficult, moving target for immune responses. But endogenous retroviral proteins cannot mutate, and if they are only expressed in HIV-infected cells it is possible that triggering immune responses against these proteins with a vaccine would provide another means of targeting and eliminating HIV-infected cells.
Brad Jones's presentation will soon be available online as part of the Monday webcast of the CROI session entitled "Host-Cell Regulation of Viral Replication" (Monday Feb 26, 10:00 AM). Abstracts and PDFs of poster presentations will start becoming available online on the conference website after the meeting ends on February 28.