PMID:23029581

Citation	Le Sommer, C, Barrows, NJ, Bradrick, SS, Pearson, JL and Garcia-Blanco, MA (2012) G protein-coupled receptor kinase 2 promotes flaviviridae entry and replication. PLoS Negl Trop Dis 6:e1820
Abstract	Flaviviruses cause a wide range of severe diseases ranging from encephalitis to hemorrhagic fever. Discovery of host factors that regulate the fate of flaviviruses in infected cells could provide insight into the molecular mechanisms of infection and therefore facilitate the development of anti-flaviviral drugs. We performed genome-scale siRNA screens to discover human host factors required for yellow fever virus (YFV) propagation. Using a 2×2 siRNA pool screening format and a duplicate of the screen, we identified a high confidence list of YFV host factors. To find commonalities between flaviviruses, these candidates were compared to host factors previously identified for West Nile virus (WNV) and dengue virus (DENV). This comparison highlighted a potential requirement for the G protein-coupled receptor kinase family, GRKs, for flaviviral infection. The YFV host candidate GRK2 (also known as ADRBK1) was validated both in siRNA-mediated knockdown HuH-7 cells and in GRK(-/-) mouse embryonic fibroblasts. Additionally, we showed that GRK2 was required for efficient propagation of DENV and Hepatitis C virus (HCV) indicating that GRK2 requirement is conserved throughout the Flaviviridae. Finally, we found that GRK2 participates in multiple distinct steps of the flavivirus life cycle by promoting both entry and RNA synthesis. Together, our findings identified GRK2 as a novel regulator of flavivirus infection and suggest that inhibition of GRK2 function may constitute a new approach for treatment of flavivirus associated diseases.
Links	PubMed PMC3441407 Online version:10.1371/journal.pntd.0001820
Keywords
edit table

Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:ARBK1		GO:0022415: negative regulation of viral reproduction	ECO:0000315:		P		Figure 3 shows that "GRK2 is required for YFV-17D propagation in mouse embryonic fibroblasts."	complete CACAO 5259
HUMAN:ARBK1		GO:0046718: viral entry into host cell	ECO:0000315:		P		Figure 5 says "GRK2 plays a role in YFV-17D entry"	complete CACAO 5261
HUMAN:ARBK1		GO:0019079: viral genome replication	ECO:0000315:		P		Figure 6 says "GRK2 plays a role in viral RNA synthesis."	complete CACAO 5262
HUMAN:ARBK1	involved_in	GO:0046718: viral entry into host cell	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:ARBK1	involved_in	GO:0019079: viral genome replication	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete

References

See Help:References for how to manage references in GONUTS.