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Rapid, Seamless Generation of Recombinant Poxviruses using Host Range and Visual Selection
Published on: May 24, 2020
Multiple phosphatidylinositol 3-kinases regulate vaccinia virus morphogenesis.
Shannon McNulty1, William Bornmann, Jill Schriewer
1Microbiology and Molecular Genetics Graduate Program, Emory University School of Medicine, Atlanta, Georgia, United States of America.
Plos One
|June 8, 2010
Summary
Phosphatidylinositol 3-kinases (PI3Ks) regulate poxvirus morphogenesis. Inhibiting PI3Ks or using PI3K-deficient cells reveals novel steps in virion development, suggesting new therapeutic targets for poxvirus containment.
Area of Science:
- Virology
- Cell Biology
- Biochemistry
Background:
- Poxvirus morphogenesis involves intricate host cell membrane wrapping.
- Phosphatidylinositol 3-kinases (PI3Ks) are known to mediate poxvirus entry.
Purpose of the Study:
- To investigate the role of PI3Ks in poxvirus morphogenesis beyond viral entry.
- To identify novel regulatory mechanisms and potential therapeutic targets for poxvirus infections.
Main Methods:
- Screening of kinase inhibitors using plaque assays.
- Analysis of viral growth curves and electron microscopy.
- Utilizing cells deficient in PI3K regulatory subunits (p85alpha(-/-)beta(-/-)).
Main Results:
- Selective PI3K inhibitors reduced poxvirus growth.
- PI3Ks regulate two distinct steps in virion morphogenesis: immature to mature virion (IMV) transition and IMV envelopment to form intracellular enveloped virions (IEVs).
- PI3K inhibition exacerbated viral defects in p85alpha(-/-)beta(-/-) cells, indicating redundant PI3K utilization.
Conclusions:
- PI3Ks play a critical, multifaceted role in poxvirus morphogenesis.
- Phosphatidylinositol dynamics mediated by PI3Ks represent a novel regulatory mechanism for virion development.
- Targeting PI3Ks offers a potential therapeutic strategy for controlling poxvirus spread.
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