title: Multiple sites in the N-terminal half of simian immunodeficiency virus capsid protein contribute to evasion from rhesus monkey TRIM5α-mediated restriction.
abstract: BACKGROUND
  We previously reported that cynomolgus monkey (CM) TRIM5α 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) TRIM5α 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 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 82nd to 99th amino acid residues) of HIV-2 CA were efficiently restricted by Rh TRIM5α. However, the corresponding loop of SIVmac239 CA alone (from the 81st to 97th amino acid residues) was not sufficient to evade Rh TRIM5α 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 TRIM5α, indicating that glutamine at the 118th of SIVmac239 CA is necessary to evade Rh TRIM5α. 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 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.
  
  
  CONCLUSIONS
  We found that multiple regions of the SIVmac CA are necessary for complete evasion from Rh TRIM5α restriction.
authors.affiliation: Department of Viral Infections, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Kono
authors.forename: Haihan
authors.initials: H
authors.lastname: Song
authors.forename: Masaru
authors.initials: M
authors.lastname: Yokoyama
authors.forename: Hironori
authors.initials: H
authors.lastname: Sato
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Shioda
authors.forename: Emi E
authors.initials: EE
authors.lastname: Nakayama
mesh_terms: D000818:Animals; D036022:Capsid Proteins / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D015498:HIV-2 / Q000235:genetics; D006801:Humans; D057131:Immune Evasion; D008253:Macaca mulatta; D008958:Models, Molecular; D020836:Protein Structure, Quaternary; D011506:Proteins / Q000276:immunology*; D011995:Recombination, Genetic; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000254:growth & development* / Q000276:immunology*; D044767:Ubiquitin-Protein Ligases; D037521:Virulence Factors / Q000276:immunology*
chemical_list: D036022:Capsid Proteins; D011506:Proteins; D037521:Virulence Factors; C482587:TRIM5(alpha) protein, rhesus monkey; D044767:Ubiquitin-Protein Ligases
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