A comparison of murine leukemia viruses that escape from human and rhesus macaque TRIM5?s.

ABSTRACT: To better understand the binding mechanism of TRIM5? to retrovirus capsid, we had previously selected N-tropic murine leukemia virus (N-MLV) mutants escaping from rhesus macaque TRIM5? (rhTRIM5?) by passaging the virus in rhTRIM5?-expressing cells and selecting for nonrestricted variants. To test the commonality of the findings from the rhTRIM5? study, we have now employed a similar genetic approach using human TRIM5? (huTRIM5?). Consistent with the rhTRIM5? study, the mapped huTRIM5? escape mutations were distributed across the capsid exterior, confirming the extended binding surface between 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 huTRIM5? escape variants showed resistance to all primate TRIM5?s tested, but two of them sacrificed viral fitness, observations that were not made in the rhTRIM5? study. Moreover, differences in amino acid changes associated with escape from hu- and rhTRIM5?s suggested a charge dependence of the restriction by different TRIM5?s. Taken together, these results suggest that the recognition of the entire capsid surface is a general strategy for TRIM5? to restrict MLV but that significantly different specific interactions are involved in the binding of TRIM5? from different species to the MLV capsid core.

SUBMITTER: Ohkura S 

PROVIDER: S-EPMC3648092 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature