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Abstract
ENDOCYTOSIS OF HIV-1 LEADS TO INFECTION IN TROPHOBLASTS: A STUDY OF HIV-1’s CELLULAR LOCALIZATION AND MECHANISM OF ENTRY
G. Vidricaire, M.R. Tardif, M.J. Tremblay
Centre de recherche en infectiologie, Université Laval, Québec, Canada
Objectives: Maternal-infant transmission of HIV-1 is the primary cause of this retrovirus infection in infants. This presentation addresses the mechanism of HIV-1 entry into trophoblastic cells leading to infection.
Methods: Trophoblastic cells were exposed to HIV-1 virions pseudotyped with VSV-G glycoprotein or HIV-1 macrophage-tropic envelope. The amount of viral entry was monitored in 1) whole cell extracts and 2) vesicular and cytoplasmic fractions. The data were compared to lymphocytes. The localization of HIV-1 in trophoblasts was investigated by confocal fluorescent microscopy upon double staining of HIV-1 and cellular markers of the endocytic pathway. The effect of cytoskeleton and endocytosis inhibitors as well as cholesterol depletion drug was tested on both viral entry and infectivity of the virus in trophoblasts.
Results: Despite low CD4 and co-receptor expression by trophoblasts, the quantity of HIV-1’s particles in these cells upon entry was comparable to lymphocytic cells. However, cell fractionation assays revealed that the majority of virions were in the vesicular fraction. Confocal microscopy showed, upon cell entry, HIV-1 migrates from the cell surface and accumulates in the centrosomal region. The virus co-localizes with GM-1 and late endosomal markers but weakly with lysosome markers. Also, cytoskeleton inhibitors and drug depletion drugs significantly affected both cell entry and infectivity. Drugs blocking endocytosis had an important effect on these processes.
Conclusion: HIV-1 enters trophoblasts mainly by endocytosis. The presence of high concentrations of viruses in the vesicular fraction may lead to transcytosis of HIV-1 thus accounting for the reported low productive HIV-1 infection in these cells. However, infection also occurs following endocytosis of HIV-1. This constitutes a novel entry route leading to infection by HIV-1.
The 2nd IAS Conference on HIV Pathogenesis and Treatment
Abstract no.
299
Suggested Citation
" G. Vidricaire, et al.
ENDOCYTOSIS OF HIV-1 LEADS TO INFECTION IN TROPHOBLASTS: A STUDY OF HIV-1’s CELLULAR LOCALIZATION AND MECHANISM OF ENTRY.
Poster:
The 2nd IAS Conference on HIV Pathogenesis and Treatment:
Abstract no.
299"
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