title: 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.
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.
authors.affiliation: Institute of Microbiology, University Medical School, Debrecen, Hungary.
authors.forename: A
authors.initials: A
authors.lastname: Bácsi
authors.forename: P
authors.initials: P
authors.lastname: Ebbesen
authors.forename: J
authors.initials: J
authors.lastname: Szabó
authors.forename: Z
authors.initials: Z
authors.lastname: Beck
authors.forename: I
authors.initials: I
authors.lastname: Andirkó
authors.forename: E
authors.initials: E
authors.lastname: Csoma
authors.forename: F D
authors.initials: FD
authors.lastname: Tóth
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015704:CD4 Antigens / Q000276:immunology; D002460:Cell Line; D003588:Cytopathogenic Effect, Viral; D015488:HIV Antigens / Q000276:immunology; D015658:HIV Infections / Q000635:transmission; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007106:Immune Sera / Q000494:pharmacology; D018445:Infectious Disease Transmission, Vertical; D008264:Macrophages / Q000821:virology; D054397:Receptors, CCR3; D019713:Receptors, CCR5 / Q000276:immunology; D019718:Receptors, CXCR4 / Q000276:immunology; D019707:Receptors, Chemokine / Q000276:immunology; D013601:T-Lymphocytes / Q000821:virology; D013997:Time Factors; D014327:Trophoblasts / Q000187:drug effects / Q000821:virology*; D020298:U937 Cells; D014721:Vesicular stomatitis Indiana virus / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D014779:Virus Replication
chemical_list: D000911:Antibodies, Monoclonal; C515350:CCR3 protein, human; D015704:CD4 Antigens; D015488:HIV Antigens; D007106:Immune Sera; D054397:Receptors, CCR3; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D019707:Receptors, Chemokine