Long-term control of HIV-1 in hemophiliacs carrying slow-progressing allele HLA-B*5101.
HLA-B*51 alleles are reported to be associated with slow disease progression to AIDS, but the mechanism underlying this association is still unclear. In the present study, we analyzed the effect of HLA-B*5101 on clinical outcome for Japanese hemophiliacs who had been infected with HIV-1 before 1985 and had been recruited in 1998 for this study. HLA-B*5101(+) hemophiliacs exhibited significantly slow progression. The analysis of HLA-B*5101-restricted HIV-1-specific cytotoxic T-lymphocyte (CTL) responses to 4 HLA-B*-restricted epitopes in 10 antiretroviral-therapy (ART)-free HLA-B*5101(+) hemophiliacs showed that the frequency of Pol283-8-specific CD8(+) T cells was inversely correlated with the viral load, whereas the frequencies of CD8(+) T cells specific for 3 other epitopes were positively correlated with the viral load. The HLA-B*5101(+) hemophiliacs whose HIV-1 replication had been controlled for approximately 25 years had HIV-1 possessing the wild-type Pol283-8 sequence or the Pol283-8V mutant, which does not critically affect T-cell recognition, whereas other HLA-B*5101(+) hemophiliacs had HIV-1 with escape mutations in this epitope. The results suggest that the control of HIV-1 over approximately 25 years in HLA-B*5101-positive hemophiliacs is associated with a Pol283-8-specific CD8(+) T-cell response and that lack of control of HIV-1 is associated with the appearance of Pol283-8-specific escape mutants.
Kawashima
Yuka
Y
Division of Viral Immunology, Center for AIDS Research, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan.
Kuse
Nozomi
N
Gatanaga
Hiroyuki
H
Naruto
Takuya
T
Fujiwara
Mamoru
M
Dohki
Sachi
S
Akahoshi
Tomohiro
T
Maenaka
Katsumi
K
Goulder
Philip
P
Oka
Shinichi
S
Takiguchi
Masafumi
M
D000483:Alleles; D044466:Asian People / Q000235:genetics; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D018450:Disease Progression; D000939:Epitopes; D015658:HIV Infections / Q000150:complications / Q000276:immunology* / Q000503:physiopathology; D020276:HIV Long-Term Survivors; D015497:HIV-1 / Q000276:immunology* / Q000502:physiology; D015235:HLA-B Antigens / Q000235:genetics* / Q000276:immunology*; D006467:Hemophilia A / Q000150:complications* / Q000276:immunology / Q000821:virology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008958:Models, Molecular; D009154:Mutation; D010455:Peptides / Q000235:genetics / Q000276:immunology; D019562:Viral Load; D014779:Virus Replication; D054302:pol Gene Products, Human Immunodeficiency Virus / Q000276:immunology*
D000939:Epitopes; D015235:HLA-B Antigens; D010455:Peptides; D054302:pol Gene Products, Human Immunodeficiency Virus
J Virol. 2008 Sep;82(17):8548-59
18596105
Transplantation. 1990 Jun;49(6):1164-7
2360256
J Virol. 2003 Jul;77(13):7492-501
12805449
J Virol. 2002 Aug;76(15):7535-43
12097566
Nat Med. 1996 Apr;2(4):405-11
8597949
Nature. 2003 Mar 20;422(6929):307-12
12646921
N Engl J Med. 1995 Jan 26;332(4):209-16
7808486
J Virol. 2003 Jun;77(12):6889-98
12768008
Nat Med. 1997 Feb;3(2):205-11
9018240
J Immunol. 2006 May 15;176(10):6130-46
16670322
J Virol. 2008 Jun;82(11):5594-605
18385228
Nature. 2009 Apr 2;458(7238):641-5
19242411
J Exp Med. 1995 Apr 1;181(4):1365-72
7699324
Immunogenetics. 2005 Nov;57(10):717-29
16215732
J Exp Med. 2006 May 15;203(5):1357-69
16682496
Science. 1996 Oct 4;274(5284):94-6
8810254
Hum Immunol. 1999 Mar;60(3):177-86
10321954
J Virol. 1994 Sep;68(9):6103-10
8057491
AIDS. 1994 Aug;8(8):1123-8
7986410
Nature. 2002 Dec 12;420(6916):678-82
12478295
Nature. 2004 Dec 9;432(7018):769-75
15592417
J Infect Dis. 1994 Jun;169(6):1236-43
7910835
J Exp Med. 2005 Mar 21;201(6):891-902
15781581
Science. 1995 Nov 10;270(5238):988-91
7481804
J Exp Med. 2009 Apr 13;206(4):909-21
19307327
Proc Natl Acad Sci U S A. 2000 Mar 14;97(6):2709-14
10694578
N Engl J Med. 1995 Jan 26;332(4):228-32
7808489
Science. 1998 Jun 19;280(5371):1884-8
9632381
Nature. 1998 Jan 22;391(6665):397-401
9450757
AIDS. 2002 May 3;16(7):961-72
11953462
J Virol. 2007 Nov;81(21):11703-12
17699580
Nat Med. 2007 Jan;13(1):46-53
17173051
J Virol. 2007 Nov;81(22):12382-93
17804494
Nat Med. 2004 Mar;10(3):282-9
14770175
Eur J Immunol. 2000 Sep;30(9):2521-30
11009085
J Virol. 2005 Aug;79(16):10218-25
16051815
J Virol. 2007 Apr;81(7):3667-72
17251285
Trends Mol Med. 2001 Sep;7(9):379-81
11530315
J Virol. 2006 Mar;80(6):3122-5
16501126
J Immunol. 1989 Jan 1;142(1):306-11
2909619
Nat Med. 1997 Feb;3(2):212-7
9018241
J Immunol. 2000 Sep 15;165(6):3260-7
10975842
J Immunol. 2005 Jan 1;174(1):36-40
15611225
J Exp Med. 2000 Jul 3;192(1):63-75
10880527
J Virol. 1995 Jan;69(1):93-100
7983771
Blood. 1999 Feb 1;93(3):936-41
9920843
J Virol. 2006 Apr;80(7):3617-23
16537629
J Virol. 1994 Jul;68(7):4650-5
8207839
J Virol. 2000 Mar;74(6):2907-12
10684310