SUMO-interacting motifs of human TRIM5? are important for antiviral activity.

ABSTRACT: Human TRIM5? potently restricts particular strains of murine leukemia viruses (the so-called N-tropic strains) but not others (the B- or NB-tropic strains) during early stages of infection. We show that overexpression of SUMO-1 in human 293T cells, but not in mouse MDTF cells, profoundly blocks N-MLV infection. This block is dependent on the tropism of the incoming virus, as neither B-, NB-, nor the mutant R110E of N-MLV CA (a B-tropic switch) are affected by SUMO-1 overexpression. The block occurred prior to reverse transcription and could be abrogated by large amounts of restricted virus. Knockdown of TRIM5? in 293T SUMO-1-overexpressing cells resulted in ablation of the SUMO-1 antiviral effects, and this loss of restriction could be restored by expression of a human TRIM5? shRNA-resistant plasmid. Amino acid sequence analysis of human TRIM5? revealed a consensus SUMO conjugation site at the N-terminus and three putative SUMO interacting motifs (SIMs) in the B30.2 domain. Mutations of the TRIM5? consensus SUMO conjugation site did not affect the antiviral activity of TRIM5? in any of the cell types tested. Mutation of the SIM consensus sequences, however, abolished TRIM5? antiviral activity against N-MLV. Mutation of lysines at a potential site of SUMOylation in the CA region of the Gag gene reduced the SUMO-1 block and the TRIM5? restriction of N-MLV. Our data suggest a novel aspect of TRIM5?-mediated restriction, in which the presence of intact SIMs in TRIM5?, and also the SUMO conjugation of CA, are required for restriction. We propose that at least a portion of the antiviral activity of TRIM5? is mediated through the binding of its SIMs to SUMO-conjugated CA.

SUBMITTER: Arriagada G 

PROVIDER: S-EPMC3072370 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature