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

Nov 12, 2017RNA (New York, N.Y.)

The double-stranded RNA binding protein Staufen1 blocks HIV-1 NC from causing stress granules and stopping protein production

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Abstract

Overexpression of the nucleocapsid (NC) protein leads to significant reductions in virus production and host cell mRNA translation.

  • NC induces the assembly of stress granules (SG) in host cells, which is resistant to blockade by the HIV-1 capsid (CA).
  • The reduction in host cell mRNA translation was confirmed through assays measuring newly synthesized proteins.
  • Coexpression of Staufen1 completely reversed the inhibition of NC-mediated SG assembly and restored global mRNA translation and virus production.
  • NC expression resulted in the phosphorylation of protein kinase R (PKR) and eIF2α, which was also inhibited by Staufen1 coexpression.
  • The findings highlight a novel role of NC in modulating the host stress response during HIV-1 replication.

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