A dominant-negative effect of cynomolgus monkey tripartite motif protein TRIM5α on anti-simian immunodeficiency virus SIVmac activity of an African green monkey orthologue

AbstractAfrican green monkey (AGM) tripartite motif protein (TRIM) 5α can inhibit both human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus SIVmac, whereas cynomolgus monkey (CM) TRIM5α can inhibit HIV-1, but not SIVmac. We previously reported that the 17-amino-acid region and an adjacent 20-amino-acid duplication in the SPRY(B30.2) domain of AGM TRIM5α determined the species specificity. In the present study, we demonstrated that CM TRIM5α had a dominant-negative effect on the anti-SIVmac activity of AGM TRIM5α. In contrast, mutant TRIM5αs lacking the 20-amino-acid duplication did not have the dominant-negative effect, even though they failed to restrict SIVmac. These results indicated that oligomerization of the SPRY domain is required for anti-SIVmac activity and suggest that tight interaction between the viral capsid and all three molecules in one TRIM5α trimer may not be necessary for restriction activity