Human Immunodeficiency Virus (HIV) and the related monkey Simian Immunodeficiency Virus (SIV) are characterized by a high mutation rate and exist as a quasispecies within an infected host. This high mutation rate coupled with strong immune selection from the host leads to the rapid accumulation of viral “immune escape” mutations, which allow the virus to sequentially evade host immune responses.

We have studied the rates of viral mutation and selection combining bioinformatic, biostatistical, and mathematical modeling approaches with both in vitro and in vivo models of infection. Using a single cycle in vitro infection, we have shown that HIV undergoes approximately 0.4 mutation events and 14 template switching (potential recombination) events each reverse transcription cycle, and that approximately 20% of mutation events occur in association with a template switching event. In vivo, we have characterized the dynamics of immune escape during the early stages of SIV infection. We find that mutant virus often incurs a significant ‘fitness cost’ in terms of reduced replicative capacity. The high mutation rate of the virus means that a variety of immune escape mutations are already present in the viral quasispecies before the selecting immune response arises. The dynamic interplay between virus and host immune system has important implications for vaccination, since enhanced immune pressure may in some circumstances merely increase viral evolution rates.