Transmission of HIV-1 infection between trophoblast placental cells and T-cells take place via an LFA-1-mediated cell to cell contact

被引:57
作者
Arias, RA [1 ]
Muñoz, LD [1 ]
Muñoz-Fernández, A [1 ]
机构
[1] Hosp Gen Univ Gregorio Maranon, Dept Inmunol, Madrid 28007, Spain
关键词
HIV; children; vertical transmission; adhesion molecules;
D O I
10.1016/S0042-6822(02)00040-5
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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. (C) 2003 Elsevier Science (USA). All rights reserved.
引用
收藏
页码:266 / 277
页数:12
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