Wild type and H43Y variant of human TRIM5alpha show similar anti-human immunodeficiency virus type 1 activity both in vivo and in vitro.

Polymorphisms in human genes have been shown to affect the rate of disease progression to acquired immune deficiency syndrome in human immunodeficiency virus type 1 (HIV-1)-infected individuals. Recently, tripartite motif 5alpha (TRIM5alpha) was identified as a factor that confers resistance to HIV-1 infection in Old World monkey cells. Subsequently, Sawyer et al. (Curr Biol 16:95-100, 2006) reported a single nucleotide polymorphism (H43Y) in the human TRIM5alpha gene and TRIM5alpha protein with 43Y was found to lose its ability to restrict HIV-1. In the present study, we reevaluated effects of this allele on in vitro anti-HIV-1 activity as well as on HIV-1 disease progression in European and Asian cohorts of HIV-1-infected individuals. Our epidemiological and molecular biological findings clearly indicate H43Y has a very minor effect on anti-HIV-1 activity of TRIM5alpha, suggesting that this allele is immaterial, at least in HIV-1-infected Europeans and Asians.