HIV-1 sexual transmission: early events of HIV-1 infection of human cervico-vaginal tissue in an optimized ex vivo model

• Published in: Mucosal immunology Vol. 3; no. 3; pp. 280 - 290
• Main Authors: Saba, E, Grivel, J-C, Vanpouille, C, Brichacek, B, Fitzgerald, W, Margolis, L, Lisco, A
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01-05-2010; Elsevier Limited
• Subjects: 631/326/596/2563; 692/698/1543/1565/1597/554/1898; 692/699/255/1901; ADP-ribosyl Cyclase 1 - immunology; ADP-ribosyl Cyclase 1 - metabolism; Allergology; Antibodies; Biomedical and Life Sciences; Biomedicine; Bystander Effect - immunology; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD4-Positive T-Lymphocytes - virology; Cervix Uteri; Female; Gastroenterology; HIV Infections - immunology; HIV Infections - metabolism; HIV Infections - transmission; HIV-1 - immunology; HIV-1 - metabolism; Humans; Immunology; Male; Membrane Glycoproteins - immunology; Membrane Glycoproteins - metabolism; Receptors, CCR5 - immunology; Receptors, CCR5 - metabolism; Receptors, CXCR4 - immunology; Receptors, CXCR4 - metabolism; Tissue Culture Techniques; Vagina; Virus Replication - immunology
• ISSN: 1933-0219; 1935-3456
• DOI: 10.1038/mi.2010.2

Infection and dissemination of human immunodeficiency virus (HIV)-1 through the female body after vaginal intercourse depends on the activation/differentiation status of mucosal CD4 T cells. In this study, we investigated this status and the susceptibility to HIV-1 infection of human cervico-vaginal tissue
ex vivo
. We found that virtually all T cells are of the effector memory phenotype with broad CC chemokine receptor 5 (CCR5) expression. As it does
in vivo
, human cervico-vaginal tissue
ex vivo
preferentially supports the productive infection of R5 HIV-1 rather than that of X4 HIV-1 in spite of the broad expression of CXC chemokine receptor 4 (CXCR4). X4 HIV-1 replicated only in the few tissues that were enriched in CD27
+
CD28
+
effector memory CD4 T cells. Productive infection of R5 HIV-1 occurred preferentially in activated CD38
+
CD4 T cells and was followed by a similar activation of HIV-1-uninfected (bystander) CD4 T cells that may amplify viral infection. These results provide new insights into the dependence of HIV-1 infection and dissemination on the activation/differentiation of cervico-vaginal lymphocytes.