A Comparison of Murine Leukemia Viruses That Escape from Human and Rhesus Macaque TRIM5 alpha s

作者：Ohkura Sadayuki; Stoye Jonathan P^*

来源：Journal of Virology, 2013, 87(11): 6455-6468.

DOI：10.1128/JVI.03425-12

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

• 出版日期2013-6
• 单位河北医科大学