Saidi, H., Magri, G., Nasreddine, N., Requena, M. & Belec, L. R5- and X4-HIV-1 use differentially the endometrial epithelial cells HEC-1A to ensure their own spread: implication for mechanisms of sexual transmission. Virology 358, 55-68

Unité INSERM U743 Equipe Immunité et Biothérapie Muqueuse, Centre de Recherches Biomédicales des Cordeliers, Paris, Cedex 06, France. <>
Virology (Impact Factor: 3.32). 03/2007; 358(1):55-68. DOI: 10.1016/j.virol.2006.07.029
Source: PubMed


The mechanism of viral transmission across the mucosal barrier is poorly understood. Using the endometrial epithelium-derived cell line HEC-1A, we found that the cells are capable of sequestering large numbers of HIV-1 particles but are refractory to cell-free viral infection. The removal of heparan sulfate moieties of cell-surface proteoglycans (HSPG) from the apical pole of HEC-1A accounted for at least 60% of both R5- and X4-HIV-1 attachment, showing their important implication in viral attachment. HEC-1A cells also have the capacity to endocytose a weak proportion of the attached virus and pass it along to underlying cells. Fucose, N-acetylglucosamine and mannosylated-residues inhibited the transcytosis of some virus isolates, suggesting that mannose receptors can be implicated on the both R5- and X4-HIV-1 transcytosis. The inhibition of HIV transcytosis by blocking CCR5 mAb suggests the implication of specific interaction between the viral gp120 and sulfated moiety of syndecans during the transcytosis of mostly R5- and X4-HIV-1. At the basolateral pole of HEC-1A, HSPG sequestered X4- and not R5-HIV-1, highlighting the important role of HEC-1A as an X4 virus reservoir. The cell-free virus particles that have transcytosed could infect activated T cells but with a weaker efficiency than virus that had not transcytosed. The specific stimulation of HEC-1A by R5-HIV-1 increased the release of monocytes/chemokines-attracting chemokines (IL-8 and GR0) and proinflammatory cytokines (TNF-beta and IL-1alpha) that enhanced the production of virus by activated T cells. This study suggests that R5 and X4 viruses can differentially use epithelial cells to ensure their own spread.

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    • "Semen-derived exosomes inhibit trans HIV-1 infection Previous studies have demonstrated the ability of female genital epithelial cells to transcytose HIV-1 particles. Aside from cell-to-cell HIV-1 transmission, trans infection may play a critical role in the propagation of sexual transmission of HIV-1 (Bobardt et al., 2007; Bomsel, 1997; Devito et al., 2000; Ganor et al., 2013; Gupta et al., 2013; Kinlock et al., 2014; Kohli et al., 2014; Saidi et al., 2007). To determine whether SE are capable of eliciting a block on HIV-1 trans infection, we utilized a trans well chamber system. "
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    • "HIV-1 internalization process in epithelial cells allows, on the one hand, the triggering of the infection, and on the other, the transmission to other cells. Hec- 1A cells have the capacity to endocytose a weak proportion of the attached virus and pass it along the underlying cells [48]. The infectivity of the virus recovered from the basolateral pole is reduced 25e50%. "
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    • "Viral inputs were normalized by qRT-PCR. It has been suggest that the infectivity of transcytosed virus is dependent on the cell type it passes through [33], however, our data shows that virus endocytosed by VK2 cells behaved similar to most previous reports [6], [8], [10], [26], [27], [29] which showed that transcytosed virus remains infectious upon release (Fig. 2D). While the exact intracellular pathways that the virus exploits remains unknown, our data suggests that following endocytosis, different intracellular pathways are utilized by the native and heat-inactivated virus and this differential trafficking will be used as a tool to identify the precise pathway that the native virus uses "
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