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Cell-free versus cell-to-cell infection by HIV-1 and HTLV-1: exploring the link among viral source, viral trafficking and viral replication.

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Dutartre H, Clavière M, Journo C, Mahieux R,


Dutartre H, Clavière M, Journo C, Mahieux R, (click to view)

Dutartre H, Clavière M, Journo C, Mahieux R,

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Journal of virology 2016 6 22() pii

Abstract

HIV-1 and HTLV-1 are complex retroviruses mainly infecting CD4(+) T lymphocytes. In addition, antigen-presenting cells such as dendritic cells (DCs) are targeted in vivo by both viruses, although to a lesser extend. Interaction of HIV-1 with DCs plays a key role in viral dissemination from the mucosa to CD4(+) T lymphocytes present in lymphoid organs. While similar mechanisms may occur for HTLV-1 as well, most HTLV-1 data were obtained from T-cell studies, and little is known regarding the trafficking of this virus in DCs. We first compared the efficiency of cell-free versus cell-associated viral sources of both retroviruses at infecting DCs. We showed that both HIV-1 and HTLV-1 cell-free particles are poorly efficient at productively infecting DCs, except if DC-SIGN has been engaged. Furthermore, while SAMHD1 accounts for restriction of cell-free HIV-1 infection, it is not involved in HTLV-1 restriction. In addition, cell-free viruses mainly lead to a non-productive DC infection leading to trans-infection of T-cell a process important for HIV-1 spread but not for that of HTLV-1. Finally, we show that T:DC cell-to-cell transfer implies viral trafficking in vesicles that may both increase productive infection of DCs ("cis-infection") and allow viral escape from immune surveillance. Altogether, these observations allowed us to draw a model on HTLV-1 and HIV-1 trafficking in DCs.

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