The HIV-1 Nef protein binds argonaute-2 and functions as a viral suppressor of RNA interference

Aqil, Madeeha, Naqvi, Afsar Raza, Bano, Aalia and Jameel, Shahid (2013) The HIV-1 Nef protein binds argonaute-2 and functions as a viral suppressor of RNA interference. PLoS ONE, 8 (9). ISSN 1932-6203

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The HIV-1 accessory protein Nef is an important virulence factor. It associates with cellular membranes and modulates the endocytic machinery and signaling pathways. Nef also increases the proliferation of multivesicular bodies (MVBs), which are sites for virus assembly and budding in macrophages. The RNA interference (RNAi) pathway proteins Ago2 and GW182 localize to MVBs, suggesting these to be sites for assembly and turnover of the miRNA-induced silencing complex (miRISC). While RNAi affects HIV replication, it is not clear if the virus encodes a suppressor activity to overcome this innate host response. Here we show that Nef colocalizes with MVBs and binds Ago2 through two highly conserved Glycine-Tryptophan (GW) motifs, mutations in which abolish Nef binding to Ago2 and reduce virus yield and infectivity. Nef also inhibits the slicing activity of Ago2 and disturbs the sorting of GW182 into exosomes resulting in the suppression of miRNA-induced silencing. Thus, besides its other activities, the HIV-1 Nef protein is also proposed to function as a viral suppressor of RNAi (VSR).

Item Type: Article
Schools and Departments: Brighton and Sussex Medical School > Clinical and Experimental Medicine
Subjects: R Medicine
R Medicine > R Medicine (General)
R Medicine > R Medicine (General) > R852 Research. Experimentation
Depositing User: Sandy Gray
Date Deposited: 27 Feb 2018 13:44
Last Modified: 27 Feb 2018 13:44

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