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Michael Linde

I feel like this is a really exciting prospect for a therapeutic vaccine. I suppose one of the key questions, though, is the timing of HERV protein expression compared with HIV release. If infected cells express HERV sequences and these are presented within the first 24 hours after fusion, then a cellular response against the HERV sequences might kill the infected cell prior to HIV budding. If HERV sequences are delayed for some reason (which would be surprising if the transcription factors activating HIV also activate HERVs), then a cell-medicated response might be too late.

The other concern would obviously be if an anti-HERV response resulted in an unintended autoimmune reaction. HERV sequences may be activated in other conditions. Given the state of therapeutic vaccines, though, I would think this is worth the risk.

Richard Jefferys

Good question, I'd imagine Doug Nixon's group is looking at the issue of the timing of expression. I guess the lack of apparent ill-effects in the people with HERV-specific T cell responses may offer some reassurance in terms of safety but it would be useful if any therapeutic interventions could be explored in animal models first (I think macaques do have some HERVs but I'm not sure if their expression has been studied in SIV). The second paper, from AIDS, reports that HERV-K102 activity can also be detected in people with herpes and hepatitis B&C viremia, not just in people with HIV viremia, which complicates the story somewhat.

Dr. Marian Laderoute

HERV-K102 particle production was detected in the plasma from 2 of 4 normal cord blood samples. Also in this paper we showed particle production with disease activity and not when recovered (CFS-ME, MS, and acute EBV infection). HERV-K102 replication occurs in human monocytes and can be regulated by cytokines. It is unlikely that permanent T cell and antibody responses could be induced by vaccines. But there may be protection in the short term (a few months?). We suggested protection by HERV-K102 might relate to its foamy retrovirus like properties and ability to undergo lytic infections in virally infected cells or in transformed cells.

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