Selection Forces and Constraints on Retroviral Sequence Variation

All retroviruses possess a highly error-prone reverse transcriptase, but the extent of the consequent sequence diversity and the rate of evolution differ greatly among retroviruses. Because of the high mutability of retroviruses, 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 selection forces that act on these variants. Here, we suggest that two selection forces--the immune response and the limited availability of appropriate target cells during transmission and persistence--are chiefly responsible for the observed sequence diversity in untreated retroviral infections. We illustrate these aspects of positive selection by reference to specific lentiviruses human and simian immunodeficiency viruses (HIV and SIV) and oncoviruses feline leukemia virus (FeLV) and human T cell leukemia virus (HTLV) that differ in their extent of variation and in disease outcomes.