PERMISSIVE CYTOMEGALOVIRUS-INFECTION OF PRIMARY VILLOUS TERM AND FIRST-TRIMESTER TROPHOBLASTS

Forty percent of women with primary cytomegalovirus (CMV) infections d uring pregnancy infect their fetuses with complications for the baby v arying from mild to severe. How CMV crosses the syncytiotrophoblast, t he barrier between maternal blood and fetal tissue in the villous plac enta, is unknown. Virus may cross by infection of maternal cells that pass through physical breaches in the syncytiotrophoblast or by direct infection of the syncytiotrophoblast, with subsequent transmission to underlying fetal placental cells. In this study, we show that pure (> 99.99%), long-term and healthy (>3 weeks) cultures of syncytiotrophob lasts are permissively infected with CMV. Greater than 99% of infectio us progeny virus remained cell associated throughout culture periods u p to 3 weeks. Infection of term trophoblasts required a higher virus i noculum, was less efficient, and progressed more slowly than parallel infections of placental and human embryonic lung fibroblasts. Three la boratory strains (AD169, Towne, and Davis) and a clinical isolate from a congenitally infected infant all permissively infected trophoblasts , although infection efficiencies varied. The infection of first trime ster syncytiotrophoblasts with strain AD169 occurred at higher frequen cy and progressed more rapidly than infection of term cells but less e fficiently and rapidly than infection of fibroblasts. These results sh ow that villous syncytiotrophoblasts can be permissively infected by C MV but that the infection requires high virus titers and proceeds slow ly and that progeny virus remains predominantly cell associated.