A specific region of 37 amino acid residues in the SPRY (B30.2) domain of African green monkey TRIM5α determines species-specific restriction of simian immunodeficiency

Human immunodeficiency virus type 1 (HIV-1) efficiently enters cells of Old World monkeys but encounters a block before reverse transcription. This restriction is mediated by a dominant repressive factor. Recently, a member of the tripartite motif (TRIM) family proteins, TRIM5 alpha, was identified as a blocking factor in a rhesus macaque cDNA library. Among Old World monkey cell lines, the African green monkey kidney cell line CV1 is highly resistant to not only HIV-1 but also simian immunodeficiency virus SIVmac infection. We analyzed TRIM5 alpha of CV1 cells and HSC-F cells, a T-cell line from a cynomolgus monkey, and found that both CV1- and HSC-F-TRIM5 alpha s could inhibit CD4-dependent HIV-1 infection, as well as vesicular stomatitis virus glycoprotein-mediated infection. CV1-TRIM5 alpha could also inhibit SIVmac infection, whereas HSC-F-TRIM5 alpha could not. In the SPRY (B30.2) domain of CV1-TRIM5 alpha, there was a 20-amino-acid duplication that was not present in HSC-F-TRIM5 alpha. A chimeric TRIM5 alpha containing 37 amino acid residues from CV1-TRIM5 alpha, which spanned the 20-amino-acid duplication, in the background of HSC-F-TRIM5 alpha fully gained the ability to inhibit SIVmac infection. Conversely, the mutant CVI-TRIM5 alpha lacking the 20-amino-acid duplication completely lost the ability to restrict SIVmac infection. These findings clearly indicated that a specific region of 37 amino acid residues in the SPRY domain of CV1-TRIM5 alpha contained a determinant of species-specific restriction of SIVmac.