Sindbis virus usurps the cellular HuR protein to stabilize its transcripts and promote productive infections in mammalian and mosquito cells.
How 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.
Sokoloski
Kevin J
KJ
Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523-1682, USA.
Dickson
Alexa M
AM
Chaskey
Emily L
EL
Garneau
Nicole L
NL
Wilusz
Carol J
CJ
Wilusz
Jeffrey
J
D020413:3' Untranslated Regions / Q000502:physiology; D000330:Aedes / Q000821:virology; D018354:Alphavirus Infections / Q000821:virology*; D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism / Q000502:physiology*; D002460:Cell Line; D003593:Cytoplasm / Q000378:metabolism / Q000821:virology; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; D054884:Host-Pathogen Interactions; D006801:Humans; D020871:RNA Stability; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D012845:Sindbis Virus / Q000472:pathogenicity / Q000502:physiology*; D014779:Virus Replication
D020413:3' Untranslated Regions; D000954:Antigens, Surface; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; D012367:RNA, Viral; D016601:RNA-Binding Proteins