PMID:23175377

Citation	Borst, EM, Kleine-Albers, J, Gabaev, I, Babic, M, Wagner, K, Binz, A, Degenhardt, I, Kalesse, M, Jonjic, S, Bauerfeind, R and Messerle, M (2013) The human cytomegalovirus UL51 protein is essential for viral genome cleavage-packaging and interacts with the terminase subunits pUL56 and pUL89. J. Virol. 87:1720-32
Abstract	Cleavage of human cytomegalovirus (HCMV) genomes as well as their packaging into capsids is an enzymatic process mediated by viral proteins and therefore a promising target for antiviral therapy. The HCMV proteins pUL56 and pUL89 form the terminase and play a central role in cleavage-packaging, but several additional viral proteins, including pUL51, had been suggested to contribute to this process, although they remain largely uncharacterized. To study the function of pUL51 in infected cells, we constructed HCMV mutants encoding epitope-tagged versions of pUL51 and used a conditionally replicating virus (HCMV-UL51-ddFKBP), in which pUL51 levels could be regulated by a synthetic ligand. In cells infected with HCMV-UL51-ddFKBP, viral DNA replication was not affected when pUL51 was knocked down. However, no unit-length genomes and no DNA-filled C capsids were found, indicating that cleavage of concatemeric HCMV DNA and genome packaging into capsids did not occur in the absence of pUL51. pUL51 was expressed mainly with late kinetics and was targeted to nuclear replication compartments, where it colocalized with pUL56 and pUL89. Upon pUL51 knockdown, pUL56 and pUL89 were no longer detectable in replication compartments, suggesting that pUL51 is needed for their correct subnuclear localization. Moreover, pUL51 was found in a complex with the terminase subunits pUL56 and pUL89. Our data provide evidence that pUL51 is crucial for HCMV genome cleavage-packaging and may represent a third component of the viral terminase complex. Interference with the interactions between the terminase subunits by antiviral drugs could be a strategy to disrupt the HCMV replication cycle.
Links	PubMed PMC3554196 Online version:10.1128/JVI.01955-12
Keywords	Cells, Cultured; Cytomegalovirus/enzymology; Cytomegalovirus/physiology; DNA, Viral/metabolism; Endodeoxyribonucleases/genetics; Endodeoxyribonucleases/metabolism; Humans; Hydrolysis; Viral Proteins/genetics; Viral Proteins/metabolism; Viral Structural Proteins/genetics; Viral Structural Proteins/metabolism; Virus Assembly
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HCMVA:TRM2		GO:0019073: viral DNA genome packaging	ECO:0000315:		P		Figure 2A and 2B. In the absence of pUL51 DNA was not packaged in to viral capsids.	complete CACAO 7535
HCMVA:TRM2		GO:0019071: viral DNA cleavage involved in viral genome maturation	ECO:0000315:		P		Figure 1B shows that pUL51 is necessary for cleavage of catemeric DNA genome.	complete CACAO 7536
HCMVA:TRM2	involved_in	GO:0019073: viral DNA genome packaging	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete

References

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