An Antiviral Response Directed by PKR Phosphorylation of the RNA Helicase A

作者：Sadler Anthony J^*; Latchoumanin Olivier; Hawkes David; Mak Johnson; Williams Bryan R G

来源：PLoS Pathogens, 2009, 5(2): e1000311.

DOI：10.1371/journal.ppat.1000311

The double-stranded RNA- activated protein kinase R (PKR) is a key regulator of the innate immune response. Activation of PKR during viral infection culminates in phosphorylation of the a subunit of the eukaryotic translation initiation factor 2 (eIF2 alpha) to inhibit protein translation. A broad range of regulatory functions has also been attributed to PKR. However, as few additional PKR substrates have been identified, the mechanisms remain unclear. Here, PKR is shown to interact with an essential RNA helicase, RHA. Moreover, RHA is identified as a substrate for PKR, with phosphorylation perturbing the association of the helicase with double-stranded RNA (dsRNA). Through this mechanism, PKR can modulate transcription, as revealed by its ability to prevent the capacity of RHA to catalyze transactivating response (TAR)-mediated type 1 human immunodeficiency virus (HIV-1) gene regulation. Consequently, HIV-1 virions packaged in cells also expressing the decoy RHA peptides subsequently had enhanced infectivity. The data demonstrate interplay between key components of dsRNA metabolism, both connecting RHA to an important component of innate immunity and delineating an unanticipated role for PKR in RNA metabolism.

• 出版日期2009-2
• 单位河北医科大学