Multiple sites in the N-terminal half of simian immunodeficiency virus capsid protein contribute to evasion from rhesus monkey TRIM5α-mediated restriction

• Main Authors: Kono Ken, Song Haihan, Yokoyama Masaru, Sato Hironori, Shioda Tatsuo, Nakayama Emi E
• Format: Article
• Language: English
• Published: BMC 2010-09-01
• Series: Retrovirology
• Online Access: http://www.retrovirology.com/content/7/1/72

<p>Abstract</p> <p>Background</p> <p>We previously reported that cynomolgus monkey (CM) TRIM5α could restrict human immunodeficiency virus type 2 (HIV-2) strains carrying a proline at the 120^thposition of the capsid protein (CA), but it failed to restrict those with a glutamine or an alanine. In contrast, rhesus monkey (Rh) TRIM5α could restrict all HIV-2 strains tested but not simian immunodeficiency virus isolated from macaque (SIVmac), despite its genetic similarity to HIV-2.</p> <p>Results</p> <p>We attempted to identify the viral determinant of SIVmac evasion from Rh TRIM5α-mediated restriction using chimeric viruses formed between SIVmac239 and HIV-2 GH123 strains. Consistent with a previous study, chimeric viruses carrying the loop between α-helices 4 and 5 (L4/5) (from the 82^ndto 99^thamino acid residues) of HIV-2 CA were efficiently restricted by Rh TRIM5α. However, the corresponding loop of SIVmac239 CA alone (from the 81^stto 97^thamino acid residues) was not sufficient to evade Rh TRIM5α restriction in the HIV-2 background. A single glutamine-to-proline substitution at the 118^thamino acid of SIVmac239 CA, corresponding to the 120^thamino acid of HIV-2 GH123, also increased susceptibility to Rh TRIM5α, indicating that glutamine at the 118^thof SIVmac239 CA is necessary to evade Rh TRIM5α. In addition, the N-terminal portion (from the 5^thto 12^thamino acid residues) and the 107^thand 109^thamino acid residues in α-helix 6 of SIVmac CA are necessary for complete evasion from Rh TRIM5α-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 TRIM5α.</p> <p>Conclusion</p> <p>We found that multiple regions of the SIVmac CA are necessary for complete evasion from Rh TRIM5α restriction.</p>