Impact of Rb-Binding Motifs on Cytomegalovirus Replication and Drug Susceptibility
Author Information
Author(s): Rachel B. Gill, Samuel L. Frederick, Caroll B. Hartline, Sunwen Chou, Mark N. Prichard
Primary Institution: University of Alabama School of Medicine
Hypothesis
Viruses with disrupted Rb-binding sites in the UL97 kinase might have an impaired replication phenotype or altered susceptibility to antiviral drugs.
Conclusion
Disruption of the Rb binding motifs has only minor effects on viral replication in cell culture, but affects susceptibility to the drug maribavir.
Supporting Evidence
- Recombinant viruses with mutations in Rb-binding motifs replicated well with only slight delays.
- The kinase-null virus exhibited reduced susceptibility to GCV and MBV.
- Disruption of the amino terminal LxCxE motif rendered the virus hypersensitive to MBV.
Takeaway
The study looked at how changes in a virus's proteins affect its ability to grow and respond to medicine. It found that some changes don't really hurt the virus's growth but can make it more sensitive to a specific drug.
Methodology
Recombinant viruses were engineered with point mutations in the UL97 open reading frame, and their replication kinetics and drug susceptibility were evaluated in human foreskin fibroblasts and human embryonic lung cells.
Limitations
The study cannot exclude the possibility that disruption of all three Rb-binding motifs may impact growth or that replication may be more compromised in other systems.
Statistical Information
P-Value
p<0.05
Statistical Significance
p<0.05
Digital Object Identifier (DOI)
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