Does Cytolysis by CD8+ T Cells Drive Immune Escape in HIV Infection?

被引:26
作者
Balamurali, Mehala
Petravic, Janka
Loh, Liyen [2 ]
Alcantara, Sheilajen [2 ]
Kent, Stephen J. [2 ]
Davenport, Miles P. [1 ]
机构
[1] Univ New S Wales, Ctr Vasc Res, Sch Med Sci, Complex Syst Biol Grp,Fac Med, Sydney, NSW 2052, Australia
[2] Univ Melbourne, Dept Microbiol & Immunol, Melbourne, Vic, Australia
基金
英国医学研究理事会; 澳大利亚研究理事会;
关键词
IMMUNODEFICIENCY-VIRUS-INFECTION; SIMIAN-HUMAN; IN-VIVO; ANTIRETROVIRAL THERAPY; VIRAL LOAD; VIREMIA; LYMPHOCYTES; REVERSION; MACAQUES; AIDS;
D O I
10.4049/jimmunol.1002204
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
CD8(+) "cytotoxic" T cells are important for the immune control of HIV and the closely related simian models SIV and chimeric simian-human immunodeficiency virus (SHIV), although the mechanisms of this control are unclear. One effect of CD8(+) T cell-mediated recognition of virus-infected cells is the rapid selection of escape mutant (EM) virus that is not recognized. To investigate the mechanisms of virus-specific CD8(+) T cell control during immune escape in vivo, we used a real-time PCR assay to study the dynamics of immune escape in early SHIV infection of pigtail macaques. For immune escape mediated by cytolysis, we would expect that the death rate of wild type (WT) infected cells should be faster than that of EM-infected cells. In addition, escape should be fastest during periods when the total viral load is declining. However, we find that there is no significant difference in the rate of decay of WT virus compared with EM virus. Further, immune escape is often fastest during periods of viral growth, rather than viral decline. These dynamics are consistent with an epitope-specific, MHC class I-restricted, noncytolytic mechanism of CD8(+) T cell control of SHIV that specifically inhibits the growth of WT virus in vivo. The Journal of Immunology, 2010, 185: 5093-5101.
引用
收藏
页码:5093 / 5101
页数:9
相关论文
共 42 条
[1]   Inefficient cytotoxic T lymphocyte-mediated killing of HIV-1-infected cells in vivo [J].
Asquith, B ;
Edwards, CTT ;
Lipsitch, M ;
McLean, AR .
PLOS BIOLOGY, 2006, 4 (04) :583-592
[2]   Control of viremia and prevention of clinical AIDS in rhesus monkeys by cytokine-augmented DNA vaccination [J].
Barouch, DH ;
Santra, S ;
Schmitz, JE ;
Kuroda, MJ ;
Fu, TM ;
Wagner, W ;
Bilska, M ;
Craiu, A ;
Zheng, XX ;
Krivulka, GR ;
Beaudry, K ;
Lifton, MA ;
Nickerson, CE ;
Trigona, WL ;
Punt, K ;
Freed, DC ;
Guan, LM ;
Dubey, S ;
Casimiro, D ;
Simon, A ;
Davies, ME ;
Chastain, M ;
Strom, TB ;
Gelman, RS ;
Montefiori, DC ;
Lewis, MG ;
Emini, EA ;
Shiver, JW ;
Letvin, NL .
SCIENCE, 2000, 290 (5491) :486-492
[3]   Comparative evaluation of simian, simian-human, and human immunodeficiency virus infections in the pigtail macaque (Macaca nemestrina) model [J].
Batten, CJ ;
De Rose, R ;
Wilson, KM ;
Agy, MB ;
Chea, S ;
Stratov, I ;
Montefiori, DC ;
Kent, SJ .
AIDS RESEARCH AND HUMAN RETROVIRUSES, 2006, 22 (06) :580-588
[4]   HIV nonprogressors preferentially maintain highly functional HIV-specific CD8+ T cells [J].
Betts, Michael R. ;
Nason, Martha C. ;
West, Sadie M. ;
De Rosa, Stephen C. ;
Migueles, Stephen A. ;
Abraham, Jonathan ;
Lederman, Michael M. ;
Benito, Jose M. ;
Goepfert, Paul A. ;
Connors, Mark ;
Roederer, Mario ;
Koup, Richard A. .
BLOOD, 2006, 107 (12) :4781-4789
[5]   Antiviral pressure exerted by HIV-1-specific cytotoxic T lymphocytes (CTLs) during primary infection demonstrated by rapid selection of CTL escape virus [J].
Borrow, P ;
Lewicki, H ;
Wei, XP ;
Horwitz, MS ;
Peffer, N ;
Meyers, H ;
Nelson, JA ;
Gairin, JE ;
Hahn, BH ;
Oldstone, MBA ;
Shaw, GM .
NATURE MEDICINE, 1997, 3 (02) :205-211
[6]   VIRUS-SPECIFIC CD8+ CYTOTOXIC T-LYMPHOCYTE ACTIVITY ASSOCIATED WITH CONTROL OF VIREMIA IN PRIMARY HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INFECTION [J].
BORROW, P ;
LEWICKI, H ;
HAHN, BH ;
SHAW, GM ;
OLDSTONE, MBA .
JOURNAL OF VIROLOGY, 1994, 68 (09) :6103-6110
[7]  
Brumme ZL, 2006, AIDS REV, V8, P78
[8]   Enhanced cellular immunity in macaques following a novel peptide immunotherapy [J].
Chea, S ;
Dale, CJ ;
De Rose, R ;
Rantshaw, IA ;
Kent, SJ .
JOURNAL OF VIROLOGY, 2005, 79 (06) :3748-3757
[9]   Determination of virus burst size in vivo using a single-cycle SIV in rhesus macaques [J].
Chen, Hannah Yuan ;
Di Mascio, Michele ;
Perelson, Alan S. ;
Ho, David D. ;
Zhang, Linqi .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (48) :19079-19084
[10]   HIV AND T-CELL EXPANSION IN SPLENIC WHITE PULPS IS ACCOMPANIED BY INFILTRATION OF HIV-SPECIFIC CYTOTOXIC T-LYMPHOCYTES [J].
CHEYNIER, R ;
HENRICHWARK, S ;
HADIDA, F ;
PELLETIER, E ;
OKSENHENDLER, E ;
AUTRAN, B ;
WAINHOBSON, S .
CELL, 1994, 78 (03) :373-387