HLA leaves its footprints on HIV

The reasons for the poor control of HIV infection by the mammalian immune system are gradually being unravelled. The ability of certain HIV proteins to mutate and thus to elude immune detection is increasingly seen as crucial.

Moore et al. provide new evidence for critical involvement of HLA proteins of the human histocompatibility complex in shaping variations in HIV proteins and possibly evolution of the virus itself.

During both the acute and chronic phases of HIV infection, production of cytotoxic T lymphocytes (CTLs) by the host immune system exerts a strong inhibitory effect on HIV growth and replication. Therefore, it is not surprising that there is strong selective pressure for survival of HIV mutants that escape the CTL response. Although escape from the host antibody response is well accepted, escape from CTL responses has until recently been more controversial. Objections to the idea have centred around whether a CTL response against several HIV epitopes could be undermined by escape of only one epitope. With the host immune system trying to control a swarm of rapidly replicating viruses, a viral variant that is slightly less well controlled because it carries a mutation in one of several crucial epitopes would still have a competitive edge. Often the host immune response has an unfortunate tendency to focus on a small number of “immunodominant” HIV epitopes, sometimes only one, making viral escape even easier.