Pol as a target for antibody dependent cellular cytotoxicity responses in HIV-1 infection.
Antibody-dependent cellular cytotoxicity (ADCC) may assist in preventing HIV or delaying disease progression. Most prior studies have analysed Env-specific ADCC responses. We hypothesized that effective ADCC-based immunity may target conserved internal viral proteins such as Pol. We analysed the ability overlapping Pol peptides to induce activation of NK cells via ADCC. We prospectively studied ADCC responses in 83 HIV+ subjects followed for 3 years. Pol peptides were commonly targeted by ADCC responses in these chronically infected subjects (in 32 of the 83 subjects). However, Pol-specific ADCC responses declined over time and did not correlate with delayed HIV progression, measured by either baseline CD4 T cells, CD4 T cell loss over time, baseline viral load or the need to start antiretroviral therapy. Although Pol is frequently targeted by ADCC in HIV+ subjects, the strength or specificity of Pol-specific ADCC responses needs to be modulated to be effective in delaying HIV progression.
Department of Microbiology and Immunology, University of Melbourne, Victoria 3010, Australia.
Gamze
G
Isitman
Amy W
AW
Chung
Marjon
M
Navis
Stephen J
SJ
Kent
Ivan
I
Stratov
D000328:Adult; D018791:CD4 Lymphocyte Count; D015483:HIV Antibodies / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D054302:pol Gene Products, Human Immunodeficiency Virus / Q000276:immunology*
D015483:HIV Antibodies; D054302:pol Gene Products, Human Immunodeficiency Virus
Science. 1984 May 4;224(4648):497-500
6200935
AIDS Res Hum Retroviruses. 2009 Aug;25(8):837-41
19678769
Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):4144-9
12644702
J Immunol. 1990 Nov 15;145(10):3276-82
1700004
J Virol. 1997 Feb;71(2):925-33
8995609
Curr HIV Res. 2008 Nov;6(6):515-9
18991616
Adv Pharmacol. 2000;49:41-66
11013760
Nat Rev Immunol. 2005 Nov;5(11):835-43
16239902
N Engl J Med. 2009 Dec 3;361(23):2209-20
19843557
J Clin Immunol. 2001 May;21(3):227-33
11403230
Virol J. 2009 Nov 18;6:201
19922621
Lancet. 2008 Nov 29;372(9653):1894-1905
19012957
J Virol. 2008 Jun;82(11):5450-9
18353957
FASEB J. 1996 Feb;10(2):258-66
8641559
J Exp Med. 2006 Oct 2;203(10):2339-50
17000867
J Immunol. 2005 Feb 15;174(4):2185-9
15699150
J Immunol. 2006 Sep 15;177(6):4028-36
16951366
Proc Natl Acad Sci U S A. 2005 Feb 22;102(8):2886-91
15699323
J Immunol. 1996 Sep 1;157(5):2168-73
8757343
Nature. 2007 Sep 6;449(7158):101-4
17805298
J Infect Dis. 1990 Feb;161(2):198-202
2299204
Lancet. 2008 Nov 29;372(9653):1881-1893
19012954
Nature. 1991 Oct 3;353(6343):393
1815549
Vaccine. 2005 Mar 31;23(19):2522-9
15752839
J Virol. 1998 Jan;72(1):286-93
9420226
J Virol. 2009 Mar;83(6):2645-54
19158238
J Infect Dis. 2003 Apr 1;187(7):1038-45
12660917
J Infect Dis. 2006 Dec 15;194(12):1661-71
17109337
J Virol. 2006 Sep;80(18):9217-25
16940533
J Immunol. 2009 Jan 15;182(2):1202-10
19124764
J Virol. 2001 Aug;75(15):6953-61
11435575
J Immunol. 2004 Feb 15;172(4):2401-6
14764710