Sindbis virus infection sequesters the cellular HuR protein in the cytoplasm, altering host mRNA stability, splicing, and polyadenylation, representing a novel virus-host interaction mechanism.
The impact of RNA viruses on the post-transcriptional regulation of cellular gene expression is unclear. Sindbis virus causes a dramatic relocalization of the cellular HuR protein from the nucleus to the cytoplasm in infected cells. This is due to the expression of large amounts of viral RNAs that contain high affinity HuR binding sites in their 3â UTRs effectively serving as a sponge for the HuR protein. Sequestration of HuR by Sindbis virus is associated with destabilization of cellular mRNAs that normally bind HuR and rely on it to regulate their expression. Furthermore, significant changes can be observed in nuclear alternative polyadenylation and splicing events on cellular pre-mRNAs due to sequestration of HuR protein by the 3â UTR of transcripts of this cytoplasmic RNA virus. These studies suggest a new molecular mechanism of virus-host interaction that likely has significant impact on virus replication, cytopathology and pathogenesis.
Barnhart et al. (Fri,) studied this question.