Mucosal transmission of HIV is inefficient. The virus must breach physical barriers before it infects mucosal CD4+ T cells. Low-level viral replication occurs initially in mucosal CD4+ T cells, but within days high-level replication occurs in Peyer's patches, mesenteric lymph nodes and the gut lamina propria. The viral quasispecies in a donor contracts through a genetic bottleneck in the recipient, such that infection is typically established by a single founder virus. Founder viruses in subtypes A and C mucosal transmission tend to encode gp120s with reduced numbers of N-linked glycosylation sites at specific positions throughout the V1- V4 domains, relative to typical chronically replicating isolates. The transmission advantage gained by the absence of these N-linked glycosylation sites is unknown.
Using primary [alpha]4[beta]7+/CD4+ T cells and a flow-cytometry based steady-state binding assay we have determined that the removal of transmission-associated N-linked glycosylation sites from chronic subtype A and C envelopes results in large increases in the specific reactivity of gp120 for integrin-[alpha]4[beta]7. These results suggest that the genetic bottleneck reported at the time of transmission may frequently involve a requirement for the productive infection of [alpha]4[beta]7+/CD4+ T cells. Understanding the structural features of the HIV envelope that promote reactivity with integrin [alpha]4[beta]7 receptor may help define early events in HIV transmission.
(C) 2012 Lippincott Williams & Wilkins, Inc.