Sindbis Virus Usurps the Cellular HuR Protein to Stabilize Its Transcripts and Promote Productive Infections in Mammalian and Mosquito Cells

SummaryHow viral transcripts are protected from the cellular RNA decay machinery and the importance of this protection for the virus are largely unknown. We demonstrate that Sindbis virus, a prototypical single-stranded arthropod-borne alphavirus, uses U-rich 3′ UTR sequences in its RNAs to recruit a known regulator of cellular mRNA stability, the HuR protein, during infections of both human and vector mosquito cells. HuR binds viral RNAs with high specificity and affinity. Sindbis virus infection induces the selective movement of HuR out of the mammalian cell nucleus, thereby increasing the available cytoplasmic HuR pool. Finally, knockdown of HuR results in a significant increase in the rate of decay of Sindbis virus RNAs and diminishes viral yields in both human and mosquito cells. These data indicate that Sindbis virus and likely other alphaviruses usurp the HuR protein to avoid the cellular mRNA decay machinery and maintain a highly productive infection.

► Conserved U-rich elements in the 3′ UTR of alphaviruses repress RNA decay
► The RNA stability regulator, HuR, binds to Sindbis virus and other alphavirus RNAs
► HuR relocalizes to the cytoplasm during Sindbis virus infections of human cells
► Knockdown of HuR destabilizes Sindbis virus RNAs and reduces viral titer