Impact of a single amino acid in the variable region 2 of the Old World monkey TRIM5α SPRY (B30.2) domain on anti-human immunodeficiency virus type 2 activity

Variable region 1 (V1) of the SPRY domain of TRIM5α is a major determinant for species-specific virus restriction in primates. We previously reported that a chimeric TRIM5α containing baboon V1 in the background of cynomolgus monkey TRIM5α showed potent anti-human immunodeficiency virus type 2 (HIV-2) activity. Since baboons are reportedly sensitive to HIV-2 infection, there was a discrepancy between the ability of baboon TRIM5α V1 to restrict HIV-2 and baboon sensitivity to HIV-2. In the study presented here, we examined the roles of V2 and V3 of the baboon TRIM5α SPRY domain in its anti-HIV-2 activity. A chimeric TRIM5α containing the entire baboon SPRY domain showed weak anti-HIV-2 activity. This attenuation of activity was caused by a single serine-to-proline substitution in baboon TRIM5α V2. These findings indicate that the combination of V1 with other variable regions of SPRY is important in anti-HIV-2 activity of primate TRIM5α.