RESUMEN
Cervical tissue explants (CTEs) from 22 HIV-1 seronegative women were exposed to R5 HIV-1 ex vivo. Eight CTEs were productively infected in terms of HIV-1 p24Gag release in culture supernatants, whereas 14 were not. Nonetheless, both accumulation of HIV-1gag DNA and of p24Gag(+) CD4(+) T cells and macrophages occurred in both productive and, at lower levels, in nonproductive CTEs. Nonproductive CTEs differed from productive CTEs for higher secretion of C-C motif chemokine ligand 3 (CCL3) and CCL5. A post-hoc analysis revealed that all productive CTEs were established from women in their secretory phase of the menstrual cycle, whereas nonproductive CTEs were derived from women either in their secretory (28%) or proliferative (36%) menstrual cycle phases or with an atrophic endometrium (36%). Thus, our results support the epidemiological observation that sexual HIV-1 transmission from males to women as well as from women to men is more efficient during their secretory phase of the menstrual cycle.
Asunto(s)
Linfocitos T CD4-Positivos/inmunología , Cuello del Útero/inmunología , Infecciones por VIH/transmisión , VIH-1/fisiología , Macrófagos/inmunología , Adulto , Anciano , Linfocitos T CD4-Positivos/virología , Células Cultivadas , Cuello del Útero/patología , Cuello del Útero/virología , Quimiocina CCL3/metabolismo , Quimiocina CCL5/metabolismo , ADN Viral/análisis , Femenino , Proteína p24 del Núcleo del VIH/metabolismo , Infecciones por VIH/inmunología , VIH-1/patogenicidad , Humanos , Fase Luteínica , Macrófagos/virología , Persona de Mediana Edad , Técnicas de Cultivo de Órganos , VirulenciaRESUMEN
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.
Asunto(s)
Linfocitos T CD4-Positivos/inmunología , Infecciones por VIH/inmunología , Infecciones por VIH/transmisión , VIH-1/inmunología , Replicación Viral/inmunología , ADP-Ribosil Ciclasa 1/inmunología , ADP-Ribosil Ciclasa 1/metabolismo , Efecto Espectador/inmunología , Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD4-Positivos/virología , Cuello del Útero , Femenino , Infecciones por VIH/metabolismo , VIH-1/metabolismo , Humanos , Masculino , Glicoproteínas de Membrana/inmunología , Glicoproteínas de Membrana/metabolismo , Receptores CCR5/inmunología , Receptores CCR5/metabolismo , Receptores CXCR4/inmunología , Receptores CXCR4/metabolismo , Técnicas de Cultivo de Tejidos , VaginaRESUMEN
An in vitro model was used to study the transmission of HIV-1 primary isolates with different biological phenotype to cervical and rectal non polarised bioptic fragments. The method described allowed the productive infection of both cervical and rectal tissues and the virus produced could be propagated onto peripheral blood mononuclear cell cultures. Syncytium-inducing and non-syncytium inducing viral isolates were equally able to produce infection and replication.