Recommended Citation

Mucosal transmission accounts for the majority of new human immunodeficiency virus type 1 (HIV-1) infections and results in a genetically and phenotypically homogenous founder virus population in 60-80 percent of cases. Biological properties common to these transmitted and founder (T/F) viruses but not chronic control (CC) viruses would define key targets for microbicides and vaccines. To identify such properties, we tested 45 T/F and 52 CC envelope glycoproteins (Envs) from the best studied and most prevalent HIV-1 subtypes (B and C, respectively) in various pseudotype assays to determine their receptor and coreceptor interaction, tropism for primary CD4+ T cell subsets, and sensitivity to neutralizing antibodies. T/F Envs were unable to mediate entry into cells expressing low amounts of CD4, thus macrophages and other CD4low cells likely do not support their replication during mucosal transmission. In contrast, T/F Env pseudoviruses efficiently infected primary memory CD4+ T cells with a preference for the effector rather than central memory subset, as did CC pseudoviruses. There was a trend towards increased sensitivity of T/F viruses to neutralization by antibodies targeting the CD4 binding site. All T/F Envs were able to use the coreceptor CCR5 for cell entry, whereas some CC Envs used CXCR4 alone. However, one bona fide T/F virus entered and replicated very poorly in CCR5+ cells in vitro, so efficient use of CCR5 a