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

✍ Scribed by Attila Bácsi; Peter Ebbesen; Judit Szabó; Zoltán Beck; István Andirkó; Eszter Csoma; Ferenc D. Tóth

• Publisher: John Wiley and Sons
• Year: 2001
• Tongue: English
• Weight: 308 KB
• Volume: 64
• Category: Article
• ISSN: 0146-6615
• DOI: 10.1002/jmv.1063

✦ Synopsis

Abstract

Intrauterine infection of the fetus is clearly an important mode of vertical transmission of human immunodeficiency virus type 1 (HIV‐1). The syncytiotrophoblast 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 detected in the syncytiotrophoblast layer in situ, there is conflicting evidence regarding infection of syncytiotrophoblast cells with cell‐free virus. The phenotypic mixing between HIV‐1 and vesicular stomatitis virus (VSV) has been exploited to assay the susceptibility of human term syncytiotrophoblast 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 Ada‐M strains of HIV‐1 did not infect syncytiotrophoblasts. Plating efficiency of VSV(HIV‐1~IIIB~) and VSV(HIV‐1~Ba‐L~) was 10‐fold lower on syncytiotrophoblasts than on T‐cells and macrophages, respectively. Incubation of VSV(HIV‐1~IIIB~) and VSV(HIV‐1~Ba‐L~) viruses with appropriate HIV‐1 neutralizing sera before infection strongly inhibited entry of pseudotyped VSV into syncytiotrophoblast cells. These findings demonstrated that infection of syncytiotrophoblasts 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 syncytiotrophoblast cells. Neither the anti‐CD4 nor the anti‐CXCR4, anti‐CCR5, and anti‐CCR3 MAb had any inhibitory effect on infection of syncytiotrophoblast cells with VSV(HIV‐1) pseudotypes. Results from this study suggest that cell‐free HIV‐1 can enter syncytiotrophoblasts and the susceptibility of these cells to penetration by the virus is strain dependent. Pseudotype infection merely demonstrates that the first steps in HIV‐1 replication are possible in syncytiotrophoblast cells. J. Med. Virol. 64:387–397, 2001. © 2001 Wiley‐Liss, Inc.