AEGiS-07IAC: Maternal-fetal HIV-transmission: placental cells CD4 expression and permissivity to infection with HIV.

7th International AIDS Conference

Florence, Italy — June 16-21, 1991

Maternal-fetal HIV-transmission: placental cells CD4 expression and permissivity to infection with HIV.

Int Conf AIDS 1991 Jun 16-21; 7:42 (abstract no. M.A.79)
David FJ, Tran HC, Autran B, Raphael M, Menu E, Hsi BL, Barre-Sinoussi F, Chaouat G; INSERM U 262, Clin. Univ. Baudelocque, Paris

OBJECTIVE: To investigate the molecular mechanisms allowing the transplacental passage of HIV, we studied: A- The placental Fc-Receptors (Fc-R), possibly involved in the placental passage of IgG-complexed viral particles. B- The expression of CD4 and the permissivity of placental cells to infection with HIV.

METHODS: Membrane antigen expression was detected by immuno-staining of term placental tissue sections and syncytio-trophoblast (ST)-specific antigens identified by FACS analysis, allowing an assessment of cell purity, of the enriched trophoblast population isolated and maintained in cell culture. The in vitro infection with HIV-1'bru' of these cells and of human trophoblast derived chorio-carcinoma cells were studied in direct culture as well as by coculture with PHA-stimulated PBL.

RESULTS: Several Fc-R were detected, with distinct locations in the placental tissue. After h.Ig-saturation, the ST-associated Fc-R was revealed by its higher affinity to immune-complexed Ig. The CD4 molecule was colocalised with specific trophoblast markers at the ST surface of the villi. This co-expression was corroborated by FACS, as well as by gp120 & gp160 env binding and its inhibition with anti CD4 mAbs. The in vitro infection of trophoblast cells with HIV-1'bru' was verified by PCR and confirmed by in situ hybridisation. The productive infection was tested by reverse transcriptase (RT) activity and the presence of p24 Ag in the culture supernatants. Both CD4 detection and HIV infectivity were obtained with chorio-carcinoma cell lines which can be productively infected with several HIV-1 strains and with HIV-2.

DISCUSSION: Our data strongly support the possibility that ST can be infected, which may be an important step for the intra-placental spread of HIV. Lastly, the in vitro HIV-infection of placental cells also provides a suitable model for further studies concerning placental HIV-transmission and its prevention.

Keywords: AEGIS, Disease Transmission, Vertical, HIV, CD4-Positive T-Lymphocytes, HIV-1, Antigens, CD4, HIV Infections, Trophoblasts, Receptors, HIV, RNA-Directed DNA Polymerase, Placenta, HIV Antigens, HIV-2, Receptors, Fc, Polymerase Chain Reaction, Phytohemagglutinins, Cell Line, Human, In Vitro, complications, transmission, ICA7
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MA79