Evidence for a post-entry barrier to R5 HIV-1 infection of CD4 memory T cells

被引:11
作者
Vyakarnam, A
Eyeson, J
Teo, I
Zuckerman, M
Babaahmady, K
Schuitemaker, H
Shaunak, S
Rostron, T
Rowland-Jones, S
Simmons, G
Clapham, P
机构
[1] GKT Sch Med & Dent, Rayne Inst, Dept Immunol, London SE5 9NU, England
[2] Hammersmith Hosp, Sch Med, Div Infect Dis, London, England
[3] GKT Sch Med & Dent, Publ Hlth Labs, Dept Virol, Dulwich, England
[4] Netherlands Red Cross, Blood Transfus Serv, Cent Lab, Dept Clin Viroimmunol, Amsterdam, Netherlands
[5] MRC, Human Immunol Unit, Inst Mol Med, Oxford, England
[6] UCL, Windeyer Inst, Dept Mol Pathol, Wohl Vir Ctr, London WC1E 6BT, England
关键词
beta-chemokines; CD4; HIV inhibition; memory T cells;
D O I
10.1097/00002030-200109070-00003
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Background: HIV-1 strains R5 and X4 can infect CD4 memory T cells in vivo. Anti-CD3/28 stimulation induces beta -chemokines and CCR5 down-regulation and renders these cells resistant to R5 HIV-1 infection. Here we describe an additional cellular mechanism that blocks productive R5 HIV-1 infection of CD4 memory T cells. Methods: Blood-derived CD4 memory T cells and CD4 T-cell clones were infected with primary R5 and X4 HIV-1 strains. Virus replication was correlated with CCR5 expression and beta -chemokine production. Virus entry and infectivity were measured by PCR for early and late products of HIV reverse transcription respectively. Results: R5 strains were up to 1000-fold less infectious than X4 viruses for CD4 memory T cells. This resistance was independent of CCR5 levels and of the Delta -32 mutation and the CCR2-V641/CCR5-59653T linked mutations. Blocking endogenous beta -chemokines relieved minimally this restriction. At the single cell level, CD4 memory cells were either permissive or non-permissive for R5 HIV-1 infection. R5 HIV titre was up to 10-fold lower than X4 virus titre even in a permissive clone. However, R5 viruses replicated as efficiently as X4 viruses in the permissive clone when neutralizing anti-beta chemokine antibodies were added. Non-permissive cells blocked a post-entry step of the virus life-cycle and expressed early but not late HIV transcripts. Neutralizing anti-beta chemokine antibodies promoted R5 virus replication marginally in the non-permissive clone. Conclusion: Some blood memory CD4 T cells retard R5 HIV-1 replication via endogenous beta -chemokines whereas others block productive R5 HIV-1 infection by an additional mechanism that interferes with a post-entry step of the virus life cycle. These natural barriers might contribute to lower pathogenicity of R5 HIV-1 strains for CD4 memory T cells than X4 viruses that emerge late in disease. (C) 2001 Lippincott Williams &Wilkins.
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收藏
页码:1613 / 1626
页数:14
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