INTERACTIONS BETWEEN HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 AND HUMAN CYTOMEGALOVIRUS IN HUMAN TERM SYNCYTIOTROPHOBLAST CELLS COINFECTED WITH BOTH VIRUSES

Human cytomegalovirus (HCMV) and human immunodeficiency virus type 1 ( HIV-1) may interact in the pathogenesis of AIDS, The placental syncyti otrophoblast layer serves as the first line of defense of the fetus ag ainst viruses. We analyzed the patterns of replication of HIV-1 and HC MV in singly an dually infected human term syncytiotrophoblast cells c ultured in vitro. Syncytiotrophoblast cells exhibited restricted permi ssiveness for HIV-1, while HCMV replication was restricted at the leve l of immediate-early and early gene products in the singly infected ce lls, We found that the syncytiotrophoblasts as an overlapping cell pop ulation could be coinfected with HIV-1 and HCMV. HIV-1 replication was markedly upregulated by previous or simultaneous infection of the cel ls with HCMV, whereas prior HIV-I infection of the cells converted HCM V infection from a nonpermissive to a permissive one. No simultaneous enhancement of HCMV and HIV-1 expression was observed in the dually in fected cell cultures. Major immediate-early proteins of HCMV were nece ssary for enhancement of HIV-1 replication, and interleukin-6 producti on induced by HCMV and further increased by replicating HIV-1 synergiz ed with these proteins to produce this effect. Permissive replication cycle of HCMV was induced by the HIV-1 tat gene product. We were unabl e to detect HIV-1 (HCMV) or HCMV (HIV-1) pseudotypes in supernatant fl uids from dually infected cell cultures. Our results suggest that inte ractions between HIV-1 and HCMV in coinfected syncytiotrophoblast cell s may contribute to the transplacental transmission of both viruses.