The low viral production in trophoblastic cells is due to a high endocytic internalization of the human immunodeficiency virus type 1 and can be overcome by the pro-inflammatory cytokines tumor necrosis factor-alpha and interleukin-1.
Maternal-infant transmission of human immunodeficiency virus type-1 (HIV-1) is the primary cause of this retrovirus infection in neonates. Trophoblasts have been proposed to play a critical role in modulating virus spread to the fetus. This paper addresses the mechanism of HIV-1 biology in trophoblastic cells. The trophoblastic cell lines BeWo, JAR, and JEG-3 were infected with reporter HIV-1 particles pseudotyped with envelope glycoproteins from the vesicular stomatitis virus or various strains of HIV-1. We demonstrate that despite a high internalization process of HIV-1 and no block in viral production, HIV-1 established a limited infection of trophoblasts with the production of very few progeny viruses. The factor responsible for this restriction to virus replication in such a cellular microenvironment is that the intracellular p24 is concentrated predominantly in endosomal vesicles following HIV-1 entry. HIV-1 transcription and virus production of infectious particles were both augmented upon treatment of trophoblasts with tumor necrosis factor-alpha and interleukin-1. However, the amount of progeny virions released by trophoblasts infected with native HIV-1 virions was so low even in the presence of pro-inflammatory cytokines that a co-culture step with indicator cells was necessary to detect virus production. Collectively these data illustrate for the first time that the natural low permissiveness of trophoblasts to productive HIV-1 infection is because of a restriction in the mode of entry, and such a limitation can be overcome with physiologic doses of tumor necrosis factor-alpha and interleukin-1, which are both expressed by the placenta, in conjunction with cell-cell contact. Considering that there is a linear correlation between viral load and HIV-1 vertical transmission, the environment may thus contribute to the propagation of HIV-1 across the placenta.
Vidricaire
Gaël
G
Centre de Recherche en Infectiologie, Hôpital CHUL, Centre Hospitalier Universitaire de Québec, 2705 Boulevard Laurier, Ste-Foy, Québec G1V 4G2, Canada.
Tardif
Mélanie R
MR
Tremblay
Michel J
MJ
D002460:Cell Line; D004705:Endocytosis; D005260:Female; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D016328:NF-kappa B / Q000502:physiology; D015533:Transcriptional Activation; D014327:Trophoblasts / Q000821:virology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014779:Virus Replication
D007375:Interleukin-1; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha