Cell-mediated HTLV-I infection of a cervix-derived epithelial cell line.
There is considerable evidence that sexual transmission of human T-cell leukemia virus-I (HTLV-I) is mediated by virus-infected lymphocytes in genital tract secretions. However, it is not clear whether infection occurs through lesions in the genital tract epithelium or takes place via an intact epithelium. We have carried out experiments to test the hypothesis that sexual transmission of HTLV-I is initiated by lymphocyte-mediated infection of intact genital tract epithelia. To examine this question we added either free virus or HTLV-I producing MT-2 cells to cultures of a cervix-derived epithelial cell line, MS751. Although free virus did not infect MS751 cells, MS751 cells which had been coincubated with MT-2 cells became infected. These cultures produced about 50 pg/ml of HTLV-I p24 antigen per 10(6) cells over a 24 h period on the sixth day following exposure to donor T-cells. Proviral DNA could be detected in target MS751 epithelial cells by PCR. Infection of epithelia could be blocked, in a dose-dependent manner, by the sulfated polysaccharides dextran sulfate, heparin, and fucoidan, and by the enzymes fucosidase and mannosidase, but not by a number of other agents that were tested. Since MT-2 cells were observed to attach to the epithelial monolayer, we examined the ability of agents to inhibit adhesion. Adherence was inhibited by the same agents that inhibited infection. Based on these findings, we hypothesize that sexual transmission of HTLV-I may involve lymphocyte-mediated infection of genital tract epithelia and that lymphocyte adhesion to the epithelium is a critical event in transmission of HTLV-I. We speculate that a sugar moiety on the epithelium, possibly mannose or fucose, may be involved in adhesion of T-cells to epithelial cells. As sulfated polysaccharides block both adhesion and productive infection of the epithelium, these compounds might be used as active ingredients in a vaginal formulation to help prevent HTLV-I transmission.
Zacharopoulos
V R
VR
The Population Council, 1230 York Ave, New York, NY 10021, USA.
Phillips
D M
DM
D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D002584:Cervix Uteri / Q000166:cytology / Q000821:virology*; D018920:Coculture Techniques; D016264:Dextran Sulfate / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology / Q000821:virology*; D005260:Female; D015490:HTLV-I Infections / Q000635:transmission; D006493:Heparin / Q000494:pharmacology; D015368:Human T-lymphotropic virus 1 / Q000254:growth & development*; D006801:Humans; D008214:Lymphocytes / Q000821:virology*; D011134:Polysaccharides / Q000494:pharmacology; D012749:Sexually Transmitted Diseases / Q000821:virology
D011134:Polysaccharides; D006493:Heparin; D016264:Dextran Sulfate; C007789:fucoidan