Transmission of HIV-1 infection between trophoblast placental cells and T-cells take place via an LFA-1-mediated cell to cell contact.
HIV-1 vertical transmission is thought to mainly take place by virus crossing the placental barrier. However, the mechanism by which HIV-1-infects placental cells remains to be elucidated. We have found that purified cytotrophoblasts as well as trophoblastic cell lines are susceptible to infection by different HIV-1 isolates as detected by DNA-PCR and release of infectious virus, although with very low efficiency. Purified trophoblast or trophoblastic cell lines express low levels of chemokine receptors CCR-5 and CXCR-4 but not CD4 on the cell surface. To test if those molecules were used as receptors for HIV-1 infection, placental cells were pretreated with antibodies to CD4, CC-chemokines, C-X-C chemokines. None of those treatments inhibited HIV-1 infection. In contrast, we have found that HIV-1 infection of placental cells was increased in cocultures of infected T-cell blasts and placental cells. More interestingly, antibodies to beta(2) integrins and to LFA-1 were able to significantly block infection of placental cells. Cell surface expression of ICAM-1, an adhesion molecule involved in attachment of leukocytes to placenta, was upregulated in HIV-1-infected placental cells. Placental cells were able to transfer HIV-1 infection to T-cell blasts. This transmission required cell to cell contact and was also inhibited by anti-LFA-1 antibodies. In summary our results suggest that placental trophoblast could be infected by HIV-1 by a mechanism involving T cell to placental contact. Moreover, placental infection enhanced ICAM-1 expression and leukocyte adherence, an event which was required to transfer HIV-1 infection to T cells. This provides an explanation of the virus passing through the placental barrier during in utero HIV-1 vertical transmission.
Arias
Rebeca Alonso
RA
Department of Immunology, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
Muñoz
Laura Díaz
LD
Muñoz-Fernández
Ma Angeles
MA
D015704:CD4 Antigens / Q000502:physiology; D002448:Cell Adhesion; D002450:Cell Communication; D002478:Cells, Cultured; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology*; D013601:T-Lymphocytes / Q000821:virology*; D014327:Trophoblasts / Q000821:virology*
D015704:CD4 Antigens; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1