Conserved retinoblastoma protein-binding motif in human cytomegalovirus UL97 kinase minimally impacts viral replication but affects susceptibility to maribavir.
The UL97 kinase has been shown to phosphorylate and inactivate the retinoblastoma protein (Rb) and has three consensus Rb-binding motifs that might contribute to this activity. Recombinant viruses containing mutations in the Rb-binding motifs generally replicated well in human foreskin fibroblasts with only a slight delay in replication kinetics. Their susceptibility to the specific UL97 kinase inhibitor, maribavir, was also examined. Mutation of the amino terminal motif, which is involved in the inactivation of Rb, also renders the virus hypersensitive to the drug and suggests that the motif may play a role in its mechanism of action.
Gill
Rachel B
RB
Department of Pediatrics, University of Alabama School of Medicine, Birmingham, AL, USA. rbgill@uab.edu
Frederick
Samuel L
SL
Hartline
Caroll B
CB
Chou
Sunwen
S
Prichard
Mark N
MN
D020816:Amino Acid Motifs; D001562:Benzimidazoles / Q000494:pharmacology*; D002460:Cell Line; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000187:drug effects* / Q000201:enzymology* / Q000235:genetics / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D009154:Mutation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism; D012263:Ribonucleosides / Q000494:pharmacology*; D014779:Virus Replication; D004004:Dichlororibofuranosylbenzimidazole / Q000031:analogs & derivatives
D001562:Benzimidazoles; D004791:Enzyme Inhibitors; D017853:Phosphotransferases (Alcohol Group Acceptor); D016160:Retinoblastoma Protein; D012263:Ribonucleosides; C075365:ganciclovir kinase; C400401:maribavir; D004004:Dichlororibofuranosylbenzimidazole