Using HIV-1 sequence variability to explore virus biology

Human immunodeficiency virus type 1 (HIV-1) only recently established an epidemic world-wide infection in the human population. The virus persists in the human host through active replication and is able to avoid clearance by the immune system. Active replication is an important component of the rapid evolutionary potential of HIV-1, a potential which manifests itself in the evolution of immune escape variants, drug resistant variants, and variants with the ability to use different cell surface coreceptors in conjunction with CD4. Multiple zoonotic introductions, compartmentalization of virus replication in the body, and genetic bottlenecks associated with sampling during transmission, antiretroviral therapy, and geographic and/or host population isolation further contribute to the range of sequences present in extant viruses. The sum of the history of all of these phenomena is reflected in HIV-1 sequence variability, and most of these phenomena are ongoing today. Here we review the use of HIV-1 sequence variability to explore its underlying biology.