PMID- 23536686 OWN - NLM STAT- MEDLINE DCOM- 20130730 LR - 20220129 IS - 1098-5514 (Electronic) IS - 0022-538X (Print) IS - 0022-538X (Linking) VI - 87 IP - 11 DP - 2013 Jun TI - A comparison of murine leukemia viruses that escape from human and rhesus macaque TRIM5alphas. PG - 6455-68 LID - 10.1128/JVI.03425-12 [doi] AB - To better understand the binding mechanism of TRIM5alpha to retrovirus capsid, we had previously selected N-tropic murine leukemia virus (N-MLV) mutants escaping from rhesus macaque TRIM5alpha (rhTRIM5alpha) by passaging the virus in rhTRIM5alpha-expressing cells and selecting for nonrestricted variants. To test the commonality of the findings from the rhTRIM5alpha study, we have now employed a similar genetic approach using human TRIM5alpha (huTRIM5alpha). Consistent with the rhTRIM5alpha study, the mapped huTRIM5alpha 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 huTRIM5alpha escape variants showed resistance to all primate TRIM5alphas tested, but two of them sacrificed viral fitness, observations that were not made in the rhTRIM5alpha study. Moreover, differences in amino acid changes associated with escape from hu- and rhTRIM5alphas suggested a charge dependence of the restriction by different TRIM5alphas. Taken together, these results suggest that the recognition of the entire capsid surface is a general strategy for TRIM5alpha to restrict MLV but that significantly different specific interactions are involved in the binding of TRIM5alpha from different species to the MLV capsid core. FAU - Ohkura, Sadayuki AU - Ohkura S AD - Division of Virology, MRC National Institute for Medical Research, Mill Hill, London, United Kingdom. FAU - Stoye, Jonathan P AU - Stoye JP LA - eng GR - MC_U117512710/MRC_/Medical Research Council/United Kingdom GR - U117512710/MRC_/Medical Research Council/United Kingdom PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130327 PL - United States TA - J Virol JT - Journal of virology JID - 0113724 RN - 0 (Antiviral Restriction Factors) RN - 0 (Capsid Proteins) RN - 0 (Carrier Proteins) RN - 0 (Tripartite Motif Proteins) RN - EC 2.3.2.27 (TRIM5 protein, human) RN - EC 2.3.2.27 (Ubiquitin-Protein Ligases) SB - IM MH - Animals MH - Antiviral Restriction Factors MH - Capsid Proteins/genetics/*metabolism MH - Carrier Proteins/genetics/metabolism MH - Humans MH - Leukemia Virus, Murine/genetics/*metabolism MH - Macaca mulatta MH - Models, Molecular MH - Protein Binding MH - Retroviridae Infections/genetics/*metabolism/virology MH - Tripartite Motif Proteins MH - Ubiquitin-Protein Ligases PMC - PMC3648092 EDAT- 2013/03/29 06:00 MHDA- 2013/07/31 06:00 PMCR- 2013/12/01 CRDT- 2013/03/29 06:00 PHST- 2013/03/29 06:00 [entrez] PHST- 2013/03/29 06:00 [pubmed] PHST- 2013/07/31 06:00 [medline] PHST- 2013/12/01 00:00 [pmc-release] AID - JVI.03425-12 [pii] AID - 03425-12 [pii] AID - 10.1128/JVI.03425-12 [doi] PST - ppublish SO - J Virol. 2013 Jun;87(11):6455-68. doi: 10.1128/JVI.03425-12. Epub 2013 Mar 27.