Multiple lytic origins of replication are required for optimal gammaherpesvirus fitness in vitro and in vivo.
PLoS Pathog. 12:e1005510 (2016)
An unresolved question in herpesvirus biology is why some herpesviruses contain more than one lytic origin of replication (oriLyt). Using murine gammaherpesvirus 68 (MHV-68) as model virus containing two oriLyts, we demonstrate that loss of either of the two oriLyts was well tolerated in some situations but not in others both in vitro and in vivo. This was related to the cell type, the organ or the route of inoculation. Depending on the cell type, different cellular proteins, for example Hexim1 and Rbbp4, were found to be associated with oriLyt DNA. Overexpression or downregulation of these proteins differentially affected the growth of mutants lacking either the left or the right oriLyt. Thus, multiple oriLyts are required to ensure optimal fitness in different cell types and tissues.
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Publication type
Article: Journal article
Document type
Scientific Article
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Keywords
Sarcoma-associated Herpesvirus; Dependent Dna-replication; Epstein-barr-virus; Bacterial Artificial Chromosome; Kaposis-sarcoma; Murine Gammaherpesvirus-68; Functional-characterization; Identification; Establishment; Transcription
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Language
english
Publication Year
2016
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2016
ISSN (print) / ISBN
1553-7366
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1553-7374
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Volume: 12,
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Article Number: e1005510
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Public Library of Science (PLoS)
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San Francisco
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Peer reviewed
POF-Topic(s)
30203 - Molecular Targets and Therapies
Research field(s)
Immune Response and Infection
PSP Element(s)
G-501500-006
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Erfassungsdatum
2016-04-04