title: Multiple Lytic Origins of Replication Are Required for Optimal Gammaherpesvirus Fitness In Vitro and In Vivo.
abstract: 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.
authors.affiliation: Research Unit Gene Vectors, Helmholtz Zentrum München - German Research Center for Environmental Health (GmbH), Munich, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Sattler
authors.affiliation: Research Unit Gene Vectors, Helmholtz Zentrum München - German Research Center for Environmental Health (GmbH), Munich, Germany.
authors.forename: Beatrix
authors.initials: B
authors.lastname: Steer
authors.affiliation: Research Unit Gene Vectors, Helmholtz Zentrum München - German Research Center for Environmental Health (GmbH), Munich, Germany.
authors.forename: Heiko
authors.initials: H
authors.lastname: Adler
mesh_terms: D000818:Animals; D002460:Cell Line; D004261:DNA Replication; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D018741:Replication Origin; D018144:Rhadinovirus / Q000235:genetics* / Q000502:physiology; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication
chemical_list: D004279:DNA, Viral; D014764:Viral Proteins