Selection forces and constraints on retroviral sequence variation

All retroviruses possess a highly error-prone reverse transcriptase, but th e extent of the consequent sequence diversity and the rate of evolution dif fer greatly among retroviruses. Because of the high mutability of retroviru ses, it is not the generation of new viral variants that Limits the extent of diversity and the rate of evolution of retroviruses, but rather the sele ction forces that act on these variants. Here, we suggest that two selectio n forces-the immune response and the limited availability of appropriate ta rget cells during transmission and persistence-are chiefly responsible for the observed sequence diversity in untreated retroviral infections. We illu strate these aspects of positive selection by reference to specific lentivi ruses [human and simian immunodeficiency viruses (HIV and SIV)] and oncovir uses [feline Leukemia virus (FeLV) and human T cell Leukemia virus (HTLV)] that differ in their extent of variation and in disease outcomes.