Adaptation of HIV-1 to cells expressing rhesus monkey TRIM5α

The cross-species transmission of retroviruses is limited by host restriction factors that exhibit inter-species diversity. For example, the TRIM5α proteins of Old World monkeys block the early, post-entry steps in human immunodeficiency virus (HIV-1) infection. We adapted an HIV-1 isolate to replicate in cells expressing TRIM5α(rh) from rhesus monkeys, an Old World species. A single amino acid change in the cyclophilin-binding loop of the HIV-1 capsid protein allowed virus replication in cells expressing TRIM5α(rh). The capsid of the escape virus exhibited a reduced affinity for TRIM5α(rh), but retained the ability to bind cyclophilin A efficiently. Thus, a preferred HIV-1 escape pathway involves decreased binding to TRIM5α, a capsid-destabilizing factor, and retention of binding to cyclophilin A, a capsid-stabilizing factor.