Placental macrophage contact potentiates the complete replicative cycle ofhuman cytomegalovirus in syncytiotrophoblast cells: Role of interleukin-8 and transforming growth factor-beta 1

Although syncytiotrophoblast (ST) cells can be infected by human cytomegalo virus (HCMV), in vitro studies have indicated that ST cells do not support the complete viral reproductive cycle, or HCMV replication may occur in les s than 3% of ST cells, The present study tested the possibility that placen tal macrophages might enhance activation of HCMV carried in ST cells and, f urther, that infected ST cells would be capable of transmitting virus to ne ighboring macrophages, For this purpose, we studied HCMV replication in ST cells grown alone or cocultured with uninfected placental macrophages. Our results demonstrated that HCMV gene expression in ST cells was markedly upr egulated by coculture with macrophages, resulting in release of substantial amounts of infectious virus from HCMV-infected ST cells, After having beco me permissive for viral replication, ST cells delivered HCMV to the cocultu red macrophages, as evidenced by detection of virus-specific antigens in th ese cells. The stimulatory effect of coculture on HCMV gene expression in S T cells was mediated by marked interleukin-8 (IL-8) and transforming growth factor-beta 1 (TGF-beta 1) release from macrophages, an effect caused by c ontact between the different placental cells, Our findings indicate an inte ractive role for the ST laser and placental macrophages in the disseminatio n of HCMV among placental tissue, Eventually, these interactions may contri bute to the transmission of HCMV from mother to the fetus.