title: HIV-1 induced activation of CD4+ T cells creates new targets for HIV-1 infection in human lymphoid tissue ex vivo.
abstract: 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.
authors.affiliation: Laboratory of Molecular and Cellular Biophysics, National Institute of Child Health and Human Development, Bethesda, MD 20892, USA. biancoa@mail.nih.gov
authors.forename: Angélique
authors.initials: A
authors.lastname: Biancotto
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Iglehart
authors.forename: Christophe
authors.initials: C
authors.lastname: Vanpouille
authors.forename: Cristian E
authors.initials: CE
authors.lastname: Condack
authors.forename: Andrea
authors.initials: A
authors.lastname: Lisco
authors.forename: Elke
authors.initials: E
authors.lastname: Ruecker
authors.forename: Ivan
authors.initials: I
authors.lastname: Hirsch
authors.forename: Leonid B
authors.initials: LB
authors.lastname: Margolis
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Grivel
mesh_terms: 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
chemical_list: D016655:HIV Core Protein p24; D006684:HLA-DR Antigens; D053645:Interleukin-2 Receptor alpha Subunit; C514799:p24 protein, Human Immunodeficiency Virus Type 1