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

Kono K, Song H, Yokoyama M, Sato H, Shioda T, Nakayama EE - Retrovirology (2010)

Bottom Line: 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.We found that multiple regions of the SIVmac CA are necessary for complete evasion from Rh TRIM5α restriction.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Viral Infections, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.

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.

Conclusion: We found that multiple regions of the SIVmac CA are necessary for complete evasion from Rh TRIM5α restriction.

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Alignments of amino acid sequences of the CA L4/5 region of HIV-2, SIVmac, and SIVsmm selected from the Los Alamos databases. Dots denote the amino acid identical to one of the GH123 CA and dashes denote lack of an amino acid residue that is present in GH123 and other viruses. Boxes show the site of SIVmac-specific amino acid residues. H2A, B, and U represent HIV-2 group A, B, and U, respectively. MAC represents SIVmac, and SMM denotes SIVsmm.
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Figure 8: Alignments of amino acid sequences of the CA L4/5 region of HIV-2, SIVmac, and SIVsmm selected from the Los Alamos databases. Dots denote the amino acid identical to one of the GH123 CA and dashes denote lack of an amino acid residue that is present in GH123 and other viruses. Boxes show the site of SIVmac-specific amino acid residues. H2A, B, and U represent HIV-2 group A, B, and U, respectively. MAC represents SIVmac, and SMM denotes SIVsmm.

Mentions: The differences in the L4/5 amino acid sequence among different strains of HIV-2, SIVmac, and SIVsmm are shown in Figure 8. Of these, SIVmac-specific amino acid residues are the 88th A, 90th-QQΔ-92nd, and 99th S (Figure 8 boxes). Ylinen et al. reported that SIVmac QQ LPA, the mutant SIVmac containing HIV-2-specific LPA instead of QQ at the 90th to 92nd positions, was still not restricted by Rh TRIM5α [42], suggesting that the 88th and 99th amino acids or all amino acid substitutions in L4/5 between SIVmac and HIV-2 are involved in resistance to Rh TRIM5α restriction.


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

Kono K, Song H, Yokoyama M, Sato H, Shioda T, Nakayama EE - Retrovirology (2010)

Alignments of amino acid sequences of the CA L4/5 region of HIV-2, SIVmac, and SIVsmm selected from the Los Alamos databases. Dots denote the amino acid identical to one of the GH123 CA and dashes denote lack of an amino acid residue that is present in GH123 and other viruses. Boxes show the site of SIVmac-specific amino acid residues. H2A, B, and U represent HIV-2 group A, B, and U, respectively. MAC represents SIVmac, and SMM denotes SIVsmm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2944288&req=5

Figure 8: Alignments of amino acid sequences of the CA L4/5 region of HIV-2, SIVmac, and SIVsmm selected from the Los Alamos databases. Dots denote the amino acid identical to one of the GH123 CA and dashes denote lack of an amino acid residue that is present in GH123 and other viruses. Boxes show the site of SIVmac-specific amino acid residues. H2A, B, and U represent HIV-2 group A, B, and U, respectively. MAC represents SIVmac, and SMM denotes SIVsmm.
Mentions: The differences in the L4/5 amino acid sequence among different strains of HIV-2, SIVmac, and SIVsmm are shown in Figure 8. Of these, SIVmac-specific amino acid residues are the 88th A, 90th-QQΔ-92nd, and 99th S (Figure 8 boxes). Ylinen et al. reported that SIVmac QQ LPA, the mutant SIVmac containing HIV-2-specific LPA instead of QQ at the 90th to 92nd positions, was still not restricted by Rh TRIM5α [42], suggesting that the 88th and 99th amino acids or all amino acid substitutions in L4/5 between SIVmac and HIV-2 are involved in resistance to Rh TRIM5α restriction.

Bottom Line: 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.We found that multiple regions of the SIVmac CA are necessary for complete evasion from Rh TRIM5α restriction.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Viral Infections, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.

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.

Conclusion: We found that multiple regions of the SIVmac CA are necessary for complete evasion from Rh TRIM5α restriction.

Show MeSH
Related in: MedlinePlus