Key result
Phosphorylation of NFAR proteins by PKR constitutes a novel mechanism of host defense that impedes viral replication, and depletion of NFARs renders animals highly sensitive to viral infection.
NFAR proteins constitute a novel, conserved mechanism of host defense used to detect and impede aberrant translation events during viral infection.
Here, we describe a new mechanism of host defense that involves the nuclear factors associated with dsRNA (NFAR1 [90 kDa] and NFAR2 [110 kDa]), which constitute part of the shuttling ribonuclear protein (RNP) complex. Activation of the dsRNA-activated protein kinase PKR by viral RNA enabled phosphorylation of NFAR1 and NFAR2 on Thr 188 and Thr 315, an event found to be evolutionarily conserved in Xenopus. Phosphorylated NFAR1 and NFAR2 became dissociated from nuclear factor 45 (NF45), which was requisite for NFAR reshuttling, causing the NFARs to be retained on ribosomes, associate with viral transcripts, and impede viral replication. Cre-loxP animals with depletion of the NFARs in the thymus were exquisitely sensitive to the cytoplasmic replicating virus VSV (vesicular stomatitis virus). Thus, the NFARs constitute a novel, conserved mechanism of host defense used by the cell to detect and impede aberrant translation events.
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Harashima et al. (2010) studied Viral infection. Depletion of NFARs was evaluated on Viral replication and host defense. Phosphorylation of NFAR proteins by PKR constitutes a novel mechanism of host defense that impedes viral replication, and depletion of NFARs renders animals highly sensitive to viral infection.
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