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- Title
Multiple sites in the N-terminal half of simianimmunodeficiency virus capsid protein contributeto evasion from rhesus monkey TRIM5a-mediatedrestriction.
- Authors
Kono, Ken; Song, Haihan; Yokoyama, Masaru; Sato, Hironori; Shioda, Tatsuo; Nakayama, Emi E.
- Abstract
Background: We previously reported that cynomolgus monkey (CM) TRIM5a could restrict human immunodeficiency virus type 2 (HIV-2) strains carrying a proline at the 120th position of the capsid protein (CA), but it failed to restrict those with a glutamine or an alanine. In contrast, rhesus monkey (Rh) TRIM5a could restrict all HIV-2 strains tested but not simian immunodeficiency virus isolated from macaque (SIVmac), despite its genetic similarity to HIV-2. Results: We attempted to identify the viral determinant of SIVmac evasion from Rh TRIM5a-mediated restriction using chimeric viruses formed between SIVmac239 and HIV-2 GH123 strains. Consistent with a previous study, chimeric viruses carrying the loop between a-helices 4 and 5 (L4/5) (from the 82nd to 99th amino acid residues) of HIV-2 CA were efficiently restricted by Rh TRIM5a. However, the corresponding loop of SIVmac239 CA alone (from the 81st to 97th amino acid residues) was not sufficient to evade Rh TRIM5a restriction in the HIV-2 background. A single glutamine-to-proline substitution at the 118th amino acid of SIVmac239 CA, corresponding to the 120th amino acid of HIV-2 GH123, also increased susceptibility to Rh TRIM5a, indicating that glutamine at the 118th of SIVmac239 CA is necessary to evade Rh TRIM5a. In addition, the N-terminal portion (from the 5th to 12th amino acid residues) and the 107th and 109th amino acid residues in α-helix 6 of SIVmac CA are necessary for complete evasion from Rh TRIM5a-mediated restriction. A three-dimensional model of hexameric GH123 CA showed that these multiple regions are located on the CA surface, suggesting their direct interaction with TRIM5a. Conclusion: We found that multiple regions of the SIVmac CA are necessary for complete evasion from Rh TRIM5a restriction.
- Subjects
SIV antibodies; MIRIDAE; RHESUS monkeys; GLUTAMINE; AMINO acids
- Publication
Retrovirology, 2010, Vol 7, p72
- ISSN
1742-4690
- Publication type
Article
- DOI
10.1186/1742-4690-7-72