HIV-1 induced activation of CD4+ T cells creates new targets for HIV-1 infection in human lymphoid tissue ex vivo.
We demonstrate mechanisms by which HIV-1 appears to facilitate its own infection in ex vivo-infected human lymphoid tissue. In this system, HIV-1 readily infects various CD4+ T cells, but productive viral infection was supported predominantly by activated T cells expressing either CD25 or HLA-DR or both (CD25/HLA-DR) but not other activation markers: There was a strong positive correlation (r=0.64, P=.001) between virus production and the number of CD25+/HLA-DR+ T cells. HIV-1 infection of lymphoid tissue was associated with activation of both HIV-1-infected and uninfected (bystanders) T cells. In these tissues, apoptosis was selectively increased in T cells expressing CD25/HLA-DR and p24gag but not in cells expressing either of these markers alone. In the course of HIV-1 infection, there was a significant increase in the number of activated (CD25+/HLA-DR+) T cells both infected and uninfected (bystander). By inducing T cells to express particular markers of activation that create new targets for infection, HIV-1 generates in ex vivo lymphoid tissues a vicious destructive circle of activation and infection. In vivo, such self-perpetuating cycle could contribute to HIV-1 disease.
Biancotto
Angélique
A
Laboratory of Molecular and Cellular Biophysics, National Institute of Child Health and Human Development, Bethesda, MD 20892, USA. biancoa@mail.nih.gov
Iglehart
Sarah J
SJ
Vanpouille
Christophe
C
Condack
Cristian E
CE
Lisco
Andrea
A
Ruecker
Elke
E
Hirsch
Ivan
I
Margolis
Leonid B
LB
Grivel
Jean-Charles
JC
D024201:Bystander Effect / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D002478:Cells, Cultured; D015967:Gene Expression Regulation, Viral / Q000276:immunology; D016655:HIV Core Protein p24 / Q000276:immunology; D015658:HIV Infections / Q000276:immunology* / Q000628:therapy; D015497:HIV-1 / Q000276:immunology* / Q000472:pathogenicity; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D008221:Lymphoid Tissue / Q000276:immunology* / Q000821:virology
D016655:HIV Core Protein p24; D006684:HLA-DR Antigens; D053645:Interleukin-2 Receptor alpha Subunit; C514799:p24 protein, Human Immunodeficiency Virus Type 1