A Comparison of Murine Leukemia Viruses That Escape from Human and Rhesus Macaque TRIM5αs.

To better understand the binding mechanism of TRIM5a to retrovirus capsid, we had previously selected N-tropic murine leu-kemia virus (N-MLV) mutants escaping from rhesus macaque TRIM5α (rhTRIM5α) by passaging the virus in rhTRIM5α-ex-pressing cells and selecting for nonrestricted variants. To test the commonality of the findings from the rhTRIM5α study, we have now employed a similar genetic approach using human TRIM5« (huTRIM5α). Consistent with the rhTRIM5α study, the mapped huTRIM5a escape mutations were distributed across the capsid exterior, confirming the extended binding surface be-tween virus and restriction factor. Compared to the results of the previous study, fewer escape mutations were identified, with particular mutants being repeatedly selected. Three out four huTRIM5α escape variants showed resistance to all primate TRIM5as tested, but two of them sacrificed viral fitness, observations that were not made in the rhTRIM5α study. Moreover, differences in amino acid changes associated with escape from hu- and rhTRIM5αs suggested a charge dependence of the restric-tion by different TRIM5αs. Taken together, these results suggest that the recognition of the entire capsid surface is a general strategy for TRIM5α to restrict MLV but that significantly different specific interactions are involved in the binding of TRIM5α from different species to the MLV capsid core. [ABSTRACT FROM AUTHOR]