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Identification of host trafficking genes required for HIV-1 virological synapse formation in dendritic cells

Bayliss, Rebecca, Wheeldon, James, Caucheteux, Stephan M, Niessen, Carien M and Piguet, Vincent 2020. Identification of host trafficking genes required for HIV-1 virological synapse formation in dendritic cells. Journal of Virology 94 (9) , e01597-19. 10.1128/JVI.01597-19

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Abstract

Dendritic cells (DC) are one of the earliest targets of HIV-1 infection acting as a ‘Trojan Horse', concealing the virus from the innate immune system and delivering it to T-cells via virological synapses (VS). To explicate how the virus is trafficked through the cell to the VS and evades degradation, a high-throughput siRNA screen targeting membrane trafficking proteins was performed in monocyte-derived dendritic cells (MDDC). We identified several proteins including BIN-1 and RAB7L1 that share common roles in transport from endosomal compartments. Depletion of target proteins resulted in an accumulation of virus in intracellular compartments and significantly reduced viral trans-infection via the VS. By targeting endocytic trafficking and retromer recycling to the plasma membrane, we were able to reduce the virus's ability to accumulate at budding microdomains and the VS. Thus, we identify key genes involved in a pathway within DC that is exploited by HIV-1 to traffic to the VS.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: American Society for Microbiology
ISSN: 0022-538X
Date of First Compliant Deposit: 12 March 2020
Date of Acceptance: 19 February 2020
Last Modified: 31 May 2020 16:14
URI: http://orca-mwe.cf.ac.uk/id/eprint/130356

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