The HIV-1 Nef Protein Binds Argonaute-2 and Functions as a Viral Suppressor of RNA Interference

PLoS One

Aalia Shahr Bano¹  Madeeha Aqil¹  Afsar Raza Naqvi¹  Shahid Jameel¹ 

[1] International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi, India

关键词: Exosomes;    Small interfering RNAs;    HIV-1;    MicroRNAs;    RNA interference;    Viral replication;    Yellow fluorescent protein;    Membrane proteins;   

DOI  :  10.1371/journal.pone.0074472

学科分类：医学（综合）

来源: Public Library of Science

【 摘 要 】

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).

【 授权许可】

CC BY