Multiple sites in the N-terminal half of simian immunodeficiency virus capsid protein contribute to evasion from rhesus monkey TRIM5α-mediated restriction.
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.
Kono
Ken
K
Department of Viral Infections, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
Song
Haihan
H
Yokoyama
Masaru
M
Sato
Hironori
H
Shioda
Tatsuo
T
Nakayama
Emi E
EE
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*
D036022:Capsid Proteins; D011506:Proteins; D037521:Virulence Factors; C482587:TRIM5(alpha) protein, rhesus monkey; D044767:Ubiquitin-Protein Ligases
Proc Natl Acad Sci U S A. 2002 Sep 3;99(18):11920-5
12154231
J Virol. 2006 Sep;80(17):8554-65
16912305
Virology. 2006 Sep 15;353(1):234-46
16808955
Proc Natl Acad Sci U S A. 2003 Feb 4;100(3):1298-303
12547912
Retrovirology. 2009 Aug 03;6:70
19650891
Virology. 1991 Sep;184(1):219-26
1678564
Virology. 2006 Jun 20;350(1):158-63
16647098
Proc Natl Acad Sci U S A. 2006 May 9;103(19):7465-70
16648264
Acta Microbiol Hung. 1992;39(3-4):271-9
1364232
Proc Natl Acad Sci U S A. 2005 Oct 11;102(41):14849-53
16203999
Clin Immunol. 1999 Jun;91(3):321-9
10370378
J Virol. 2005 Nov;79(22):14446-50
16254380
J Virol. 2005 Sep;79(18):11580-7
16140735
Clin Infect Dis. 2005 Jul 15;41(2):243-51
15983923
Science. 1997 Oct 31;278(5339):849-53
9346481
Int J Mol Med. 2003 May;11(5):641-4
12684704
J Virol. 2004 May;78(10):5423-37
15113921
Proc Natl Acad Sci U S A. 2004 Jul 20;101(29):10774-9
15249685
J Virol. 2009 Oct;83(20):10737-51
19656869
Nucleic Acids Res. 2005 Jan 1;33(Database issue):D233-7
15608185
Science. 2000 Jan 28;287(5453):607-14
10649986
J Virol. 2006 Oct;80(19):9754-60
16973579
Clin Microbiol Rev. 2006 Oct;19(4):728-62
17041142
Proc Natl Acad Sci U S A. 2006 Apr 4;103(14):5514-9
16540544
Virology. 1996 May 15;219(2):485-8
8638416
J Gen Virol. 1995 Nov;76 ( Pt 11):2723-30
7595379
J Mol Biol. 2009 Mar 6;386(4):1179-92
19007792
J Mol Biol. 1999 Feb 12;286(1):83-93
9931251
Proc Natl Acad Sci U S A. 2004 Jul 20;101(29):10780-5
15249687
J Comput Chem. 2008 Jul 30;29(10):1693-8
18307169
Proc Natl Acad Sci U S A. 2005 Feb 22;102(8):2832-7
15689398
Gene. 1989 Apr 15;77(1):51-9
2744487
J Virol. 2007 Oct;81(19):10362-78
17626085
Science. 2006 Oct 6;314(5796):95
17023652
J Virol. 2006 Jun;80(11):5631-6
16699044
J Virol. 2006 May;80(10):4683-90
16641261
J Virol. 2007 Jul;81(13):7280-5
17475650
Virology. 1996 Apr 15;218(2):382-8
8610465
J Virol. 2008 Dec;82(23):11682-94
18799573
Virology. 2009 May 25;388(1):160-8
19342071
J Virol. 2008 Dec;82(23):11495-502
18799578
Trends Cell Biol. 2000 Oct;10(10):429-39
10998601
AIDS Res Hum Retroviruses. 1998 Jan 1;14(1):79-82
9453254
J Virol. 2003 Jan;77(1):77-83
12477812
Vaccine. 2010 May 26;28 Suppl 2:B60-7
20510746
J Virol. 2005 Jul;79(14):8870-7
15994780
Adv Protein Chem. 2003;66:27-85
14631816
J Mol Biol. 2008 Mar 7;376(5):1493-508
18222469
J Virol. 2005 May;79(10):5996-6004
15857986
Proc Natl Acad Sci U S A. 2004 Aug 10;101(32):11827-32
15280539
Virology. 2008 Sep 30;379(2):335-41
18678385
J Virol. 1990 Feb;64(2):742-7
2296082
Nat Struct Mol Biol. 2008 Nov;15(11):1184-91
18836454
Virology. 2008 Apr 10;373(2):447-56
18201746
Nat Struct Mol Biol. 2009 Oct;16(10):1036-42
19767750
J Virol. 2005 Mar;79(5):3139-45
15709033
Curr Biol. 2005 Jan 11;15(1):73-8
15649369
J Biol Chem. 2005 Jul 22;280(29):26933-40
15897199
J Virol. 1996 Jul;70(7):4220-7
8676442
J Biomol NMR. 1999 Jun;14(2):199-200
10427751
J Virol. 2005 Jul;79(14):8969-78
15994791
Nature. 2004 Feb 26;427(6977):848-53
14985764
Virology. 2006 Jul 20;351(1):112-20
16643975
Nature. 1999 Feb 4;397(6718):436-41
9989410
Virology. 1990 Oct;178(2):527-34
2120848
Proc Natl Acad Sci U S A. 2002 Sep 3;99(18):11914-9
12154227
J Virol. 2008 Dec;82(23):11669-81
18799572
Cell. 2009 Jun 26;137(7):1282-92
19523676
J Virol. 2006 Mar;80(6):2855-62
16501094
EMBO J. 2001 May 1;20(9):2140-51
11331580
Virology. 2010 Apr 10;399(2):212-20
20110098
Retrovirology. 2005 Jun 20;2:40
15967037
EMBO J. 2003 Feb 3;22(3):385-94
12554640