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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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Related in: MedlinePlus

MT4 cells were infected with recombinant SeV expressing Rh (white circles), CM (black triangles), or CM SPRY(-) (white squares) TRIM5α. Nine hours after infection, cells were superinfected with GH123, SIVmac239 or their derivative viruses. Culture supernatants were separately assayed for levels of p25 from GH123 or p27 from SIVmac239. Error bars show actual fluctuations between levels of p25 or p27 in duplicate samples. A representative of two independent experiments is shown.
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Figure 2: MT4 cells were infected with recombinant SeV expressing Rh (white circles), CM (black triangles), or CM SPRY(-) (white squares) TRIM5α. Nine hours after infection, cells were superinfected with GH123, SIVmac239 or their derivative viruses. Culture supernatants were separately assayed for levels of p25 from GH123 or p27 from SIVmac239. Error bars show actual fluctuations between levels of p25 or p27 in duplicate samples. A representative of two independent experiments is shown.

Mentions: Previously, we evaluated the antiviral effect of CM and Rh TRIM5α and found that CM TRIM5α could restrict HIV-2 GH123 carrying P at the 120th position of CA, but failed to restrict the HIV-2 GH123 mutant in which P was replaced with Q (GH123/Q) [44] (Figure 1A). In contrast, Rh TRIM5α could restrict both viruses [34] (Figure 2A and 2B). Although CA of HIV-2 GH123 and SIVmac239 share more than 87% amino acid identity (Figure 1B), CM and Rh TRIM5αs failed to restrict SIVmac239 (Figure 2C).


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)

MT4 cells were infected with recombinant SeV expressing Rh (white circles), CM (black triangles), or CM SPRY(-) (white squares) TRIM5α. Nine hours after infection, cells were superinfected with GH123, SIVmac239 or their derivative viruses. Culture supernatants were separately assayed for levels of p25 from GH123 or p27 from SIVmac239. Error bars show actual fluctuations between levels of p25 or p27 in duplicate samples. A representative of two independent experiments is shown.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: MT4 cells were infected with recombinant SeV expressing Rh (white circles), CM (black triangles), or CM SPRY(-) (white squares) TRIM5α. Nine hours after infection, cells were superinfected with GH123, SIVmac239 or their derivative viruses. Culture supernatants were separately assayed for levels of p25 from GH123 or p27 from SIVmac239. Error bars show actual fluctuations between levels of p25 or p27 in duplicate samples. A representative of two independent experiments is shown.
Mentions: Previously, we evaluated the antiviral effect of CM and Rh TRIM5α and found that CM TRIM5α could restrict HIV-2 GH123 carrying P at the 120th position of CA, but failed to restrict the HIV-2 GH123 mutant in which P was replaced with Q (GH123/Q) [44] (Figure 1A). In contrast, Rh TRIM5α could restrict both viruses [34] (Figure 2A and 2B). Although CA of HIV-2 GH123 and SIVmac239 share more than 87% amino acid identity (Figure 1B), CM and Rh TRIM5αs failed to restrict SIVmac239 (Figure 2C).

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