Coinfection as a factor in vertical viral transmission

Abstract

Although both human immunodeficiency virus type 1 (HIV-1) and human T cell leukemia-lymphoma virus type I (HTLV-I) can enter syncytiotrophoblast (ST) cells, the trophoblast is assumed to restrict the rate of retrovirus transmission. We studied the interactions of human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) with HIV-1 and HTLV-I in human term ST cells. HCMV replication was restricted at the level of immediate-early (IE) and early (E) gene products in singly infected cells. Previous or simultaneous infection of the cells with HCMV resulted in marked upregulation of HIV-1 replication, whereas prior HIV-1 infection of the cells converted HCMV replication from nonpermissive to permissive in nature. In contrast, coinfection of ST cells with HCMV and HTLV-I resulted in simultaneous replication of both viruses. Enhancing activities between retroviruses and HCMV were mediated primarily by the Tat, Tax and IE proteins. The ST cells could be productively infected with EBV, and dual infection of the cells with EBV and HTLV-I resulted in full replication cycle of otherwise latent HTLV-I. Permissive replication cycle of HTLV-I was induced by the EBV IE gene product Zta. Our data suggest that HCMV and EBV may play a critical role in the transplacental transmission of human retroviruses.