HIV-1 NC-induced stress granule assembly and translation arrest are inhibited by the dsRNA binding protein Staufen1

• DOI: 10.1261/rna.064618.117
• Publication Date: 2017-11-11T01:25:18Z
• Authors: Shringar Rao; Alessandro Cinti; Abdelkrim Temzi; Raquel Amorim; Ji Chang You; Andrew J. Mouland
• Keywords: Stress granule; RNA Silencing

The nucleocapsid (NC) is an N-terminal protein derived from the HIV-1 Gag precursor polyprotein, pr55Gag NC possesses key functions at several pivotal stages of viral replication. For example, interaction between and host double-stranded RNA-binding Staufen1 was shown to regulate steps in replication cycle, such as multimerization genomic RNA encapsidation. In this work, we observed that overexpression leads induction stress granule (SG) assembly. NC-mediated SG assembly unique it resistant blockade imposed by capsid (CA), earlier work. also reduced cell mRNA translation, judged a puromycylation assay de novo synthesized proteins, recapitulated polysome profile analyses. Virus production found be significantly reduced. Finally, expression completely rescued assembly, global translation well virus production. resulted phosphorylation kinase R (PKR) eIF2α, inhibited with coexpression. This work sheds light on unexpected function translation. A comprehensive understanding molecular mechanisms which fine balance structural proteins CA act concert modulate response will aid development new antiviral therapeutics.