Inhibitory effect of human TRIM5alpha on HIV-1 production.

Tripartite motif-containing 5 isoform-alpha (TRIM5alpha), a host restriction factor, blocks infection of some retroviruses at a post-entry, pre-integration stage in a species-specific manner. A recent report by Sakuma et al. describes a second antiretroviral activity of rhesus macaque TRIM5alpha, which blocks HIV-1 production through rapid degradation of HIV-1 Gag polyproteins. Here, we find that human TRIM5alpha limits HIV-1 production. Transient expression of TRIM5alpha decreased HIV-1 production, whereas knockdown of TRIM5alpha in human cells increased virion release. A single amino acid substitution (R437C) in the SPRY domain diminished the restriction effect. Moderate levels of human wild-type TRIM5alpha and a little amount of R437C mutant were incorporated into HIV-1 virions. The R437C mutant also lost restriction activity against N-tropic murine leukemia virus infection. However, the corresponding R to C mutation in rhesus macaque TRIM5alpha had no effect on the restriction ability. Our findings suggest human TRIM5alpha is an intrinsic immunity factor against HIV-1 infection. The importance of arginine at 437 aa in SPRY domain for the late restriction is species-specific.