Pseudotypes of vesicular stomatitis virus-fearing envelope antigens of certain HIV-1 strains permissively infect human syncytiotrophoblasts cultured in vitro: Implications for in vivo infection syncytiotrophoblasts by cell-free HIV-1

Intrauterine infection of the fetus is clearly an important mode of vertica l transmission of human immunodeficiency virus type 1 (HIV-1). The syncytio trophoblast layer of the human placenta must be traversed by HIV-1 in order to reach underlying cells and fetal capillaries. Although HIV-1 has been d etected in the syncytiotrophoblast layer in situ, there is conflicting evid ence regarding infection of syncytiotrophoblast cells with cell-free virus. The phenotypic mixing between HIV-1 and vesicular stomatitis virus (VSV) h as been exploited to assay the susceptibility of human term syncytiotrophob last cells to penetration by various strains of HIV-1. VSV(HIV-1(IIIB)) and VSV(HIV-1(Ba-L)) pseudotypes were found to enter syncytiotrophoblast cells . In contrast, VSV pseudotyped with envelope glycoproteins of RF, MN, or Ad a-M strains of HIV-1 did nor infect syncytiotrophoblasts. Plating efficienc y of VSV(HIV-1(IIIB)) and VSV(HIV-1(Ba-L)) was 10-fold lower on syncytiotro phoblasts than on T-cells and macrophages, respectively. Incubation of VSV( HIV-1(IIIB)) and VSV(HIV-1(Ba-L)) viruses with appropriate HIV-1 neutralizi ng sera before infection strongly inhibited entry of pseudotyped VSV into s yncytiotrophoblast cells. These findings demonstrated that infection of syn cytiotrophoblasts with VSV(HIV-1) pseudotypes was mediated by Env from IIIB and Ba-L strains of HIV-1. Monoclonal antibodies (MAb) to CD4, CXCR4, CCR5 , and CCR3 were tested for their ability to block VSV(HIV-1) infection of s yncytiotrophoblast cells. Neither the anti-CD4, nor the anti-CXCR4, anti-CC R5, and anti-CCR3 MAb had any inhibitory effect on infection of syncytiotro phoblast cells with VSV(HIV-1) pseudotypes. Results from th is study sugges t that cell-free HIV-1 can enter syncytiotrophoblasts and the susceptibilit y of these cells to penetration by the virus is strain dependent. Pseudotyp e infection merely demonstrates that the first steps in HIV-1 replication a re possible in syncytiotrophoblast cells. J. Med. Virol. 64:387-397, 2001. (C) 2001 Wiley-Liss, Inc.