HIV-1 Infection of the Trophoblast Cell Line BeWo: A Study of Virus Uptake

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Abstract
An in vitro model has made it possible to demonstrate HIV transmission from infected lymphocytes to placental trophoblast cells via endocytosis. Upon addition to cultured trophoblast cells (BeWo), chronically HIV-infected lymphocytic cells (MOLT-4) adhered to the epithelial cells via a complex of newly induced microvilli. Though viruses were infrequently seen in the infected lymphocytic cell line, mature virions appeared promptly and profusely in the interstices between the interdigitating microvilli of the two cell types. Virions appeared to bud from the lymphocyte donor cells at the point of cell-to-cell contact and were rapidly taken up by the trophoblast cells via an endocytic mechanism involving coated pits, endosomes, and lysosomes. Electron microscopic observations suggest that HIV may later escape into the trophoblast cytoplasm by fusing with the endosome membrane or by lysing the lysosome membrane. Coincubation for 1 h was sufficient to establish HIV infection in the trophoblast cell line. Four weeks after thoroughly washing out the donor lymphocytic cells, HIV RNA was demonstrated in clusters of BeWo cells by in situ hybridization, and p24 antigen was localized with immunocytochemistry. Soluble CD4 did not block infection as measured by p24 ELISA. The HIV infection was productive and chronic as demonstrated by cocultivating the BeWo cells with indicator lymphocytes 4 weeks after the initial infection. This study, demonstrating a mechanism of HIV transmission, expands upon previous observations that trophoblast cell lines lacking the CD4 viral receptor can nevertheless be infected by HIV and can support productive infection.