PMID:22022269

Citation	Yu, SF, Lujan, P, Jackson, DL, Emerman, M and Linial, ML (2011) The DEAD-box RNA helicase DDX6 is required for efficient encapsidation of a retroviral genome. PLoS Pathog. 7:e1002303
Abstract	Viruses have to encapsidate their own genomes during the assembly process. For most RNA viruses, there are sequences within the viral RNA and virion proteins needed for high efficiency of genome encapsidation. However, the roles of host proteins in this process are not understood. Here we find that the cellular DEAD-box RNA helicase DDX6 is required for efficient genome packaging of foamy virus, a spumaretrovirus. After infection, a significant amount of DDX6, normally concentrated in P bodies and stress granules, re-localizes to the pericentriolar site where viral RNAs and Gag capsid proteins are concentrated and capsids are assembled. Knockdown of DDX6 by siRNA leads to a decreased level of viral nucleic acids in extracellular particles, although viral protein expression, capsid assembly and release, and accumulation of viral RNA and Gag protein at the assembly site are little affected. DDX6 does not interact stably with Gag proteins nor is it incorporated into particles. However, we find that the ATPase/helicase motif of DDX6 is essential for viral replication. This suggests that the ATP hydrolysis and/or the RNA unwinding activities of DDX6 function in moderating the viral RNA conformation and/or viral RNA-Gag ribonucleoprotein complex in a transient manner to facilitate incorporation of the viral RNA into particles. These results reveal a unique role for a highly conserved cellular protein of RNA metabolism in specifically re-locating to the site of viral assembly for its function as a catalyst in retroviral RNA packaging.
Links	PubMed PMC3192847 Online version:10.1371/journal.ppat.1002303
Keywords	Adenosine Triphosphate/metabolism; Capsid Proteins/genetics; Capsid Proteins/metabolism; Cell Line; DEAD-box RNA Helicases/genetics; DEAD-box RNA Helicases/metabolism; Gene Products, gag/metabolism; Genome, Viral; HEK293 Cells; Humans; Proto-Oncogene Proteins/genetics; Proto-Oncogene Proteins/metabolism; RNA Interference; RNA, Small Interfering; RNA, Viral/genetics; RNA, Viral/metabolism; Spumavirus/genetics; Spumavirus/physiology; Viral Proteins/genetics; Viral Proteins/metabolism; Virus Assembly
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:DDX6		GO:0000932: cytoplasmic mRNA processing body	ECO:0000315:		C		Fig. 2AB	complete CACAO 2728
HUMAN:DDX6		GO:0019074: viral RNA genome packaging	ECO:0000315:		P		Fig. 5BC	complete CACAO 2729
HUMAN:DDX6	part_of	GO:0000932: P-body	ECO:0000315: mutant phenotype evidence used in manual assertion		C		Seeded From UniProt	complete
HUMAN:DDX6	involved_in	GO:0019074: viral RNA genome packaging	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
FOAMV:GAG		GO:0044163: host cytoskeleton	ECO:0000315:		C		Fig. 2CD and Fig. 4EF	complete CACAO 2725
FOAMV:GAG	part_of	GO:0044163: host cytoskeleton	ECO:0000315: mutant phenotype evidence used in manual assertion		C		Seeded From UniProt	complete

References

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