Submitted May 29, 2007
Accepted September 22, 2007
HIV-1-induced activation of CD4+ T cells creates new targets for HIV-1 infection in human lymphoid tissue ex vivo
Angelique Biancotto*, Sarah J. Iglehart, Christophe Vanpouille, Cristian E. Condack, Andrea Lisco, Elke Ruecker, Ivan Hirsch, Leonid B. Margolis, and Jean-Charles Grivel
Laboratory of Molecular and Cellular Biophysics, National Institute of Child Health and Human Development, Bethesda, MD, United States
INSERM UMR599, Centre de Recherche en Cancerologie de Marseille, Institut Paoli-Calmettes, Universite Mediterranee, Marseille, France
* Corresponding author; email: biancoa{at}mail.nih.gov.
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 = 0.0001) 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.
