CAT-transfected epithelial cells provide evidence for a CD4 independent pathway of HIV infection

Several laboratories have presented evidence that HIV can productively infect CD4- cell lines. However, this data could be challenged on the basis that the target cells may express low levels of the CD4 receptor. In addition, it could be argued that assays might be detecting residual virus. In the case of cell-mediated infection, it is possible that virus detected in assays could be secreted from HIV-infected donor cells rather than the target CD4- cells. In this report we describe a CD4- epithelial cell line which has been transfected with a plasmid containing the chloramphenicol acetyltransferase (CAT) gene ligated to the HIV LTR. CAT-ELISA and immunocytochemistry indicate that target cells synthesize CAT after exposure to HIV-infected primary activated peripheral blood mononuclear cells (PBMC). Results correlate very well with p24 ELISA assays. Infection of epithelia by primary NSI strains of HIV can be blocked by patient antisera or by certain sulfated polysaccharides. Since the CAT assay is not dependent on virus production, the data reported here confirm that CD4- epithelial cells derived from the human cervix can be productively infected by HIV. The observations also support the theory that sexual transmission of HIV could be initiated by infection of genital tract epithelia. Furthermore, the findings support the suppositions that sexual transmission of HIV could be prevented by antibodies to HIV or alternately by a topical formulation containing certain sulfated polysaccharides.