EVOLUTION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ENVELOPE SEQUENCES IN INFECTED INDIVIDUALS WITH DIFFERING DISEASE PROGRESSION PROFILES

Sequence Variation displayed by the human immunodeficiency virus type 1 (HIV-1) has been proposed to be linked to the pathogenesis of acquir ed immunodeficiency syndrome (AIDS). To assess viral evolution during the course of infection, we evaluated sequence variability in the env variable domains in four HIV-1-infected individuals exhibiting differi ng profiles of CD4(+) T cell decline when followed from seroconversion until the development of AIDS or loss of followup. Proviral sequences encoding the V3-V5 region of gp120 were obtained following PGR amplif ication of peripheral blood mononuclear cell DNA and cloning. Virus in each patient was relatively homogeneous early in infection and then d iverged with time, more consistently at its nonsynonymous sites. Just prior to or coincident with a rapid decline in CD4(+) T cell numbers, sequences were found with basic amino acid substitutions clustered wit hin and downstream of the gp120 V3 domain. Within the constraints of t he current dataset, we conclude that the virus appears to continually accumulate changes in its amino acid sequences well into the time of m arked CD4(+) T cell decline. (C) 1998 Academic Press.