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

Abstract

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.

• Authors: E Saba, J-C Grivel, C Vanpouille, B Brichacek, W Fitzgerald, L Margolis, A Lisco
• Journal: Mucosal immunology (Mucosal Immunol) Vol. 3 Issue 3 Pg. 280-90 (May 2010) ISSN: 1935-3456 [Electronic] United States
• PMID: 20147895 (Publication Type: Journal Article, Research Support, N.I.H., Intramural)

Chemical References

• CXCR4 protein, human
• Membrane Glycoproteins
• Receptors, CCR5
• Receptors, CXCR4
• CD38 protein, human
• ADP-ribosyl Cyclase 1

Topics

• ADP-ribosyl Cyclase 1 (immunology, metabolism)
• Bystander Effect (immunology)
• CD4-Positive T-Lymphocytes (immunology, metabolism, virology)
• Cervix Uteri
• Female
• HIV Infections (immunology, metabolism, transmission)
• HIV-1 (immunology, metabolism)
• Humans
• Male
• Membrane Glycoproteins (immunology, metabolism)
• Receptors, CCR5 (immunology, metabolism)
• Receptors, CXCR4 (immunology, metabolism)
• Tissue Culture Techniques
• Vagina
• Virus Replication (immunology)