title: Vaccinia-virus-induced cellular contractility facilitates the subcellular localization of the viral replication sites.
abstract: Poxviruses, such as vaccinia virus (VV), replicate their DNA in endoplasmic-reticulum-enclosed cytoplasmic sites. Here, we compare the dynamics of the VV replication sites with those of the attenuated strain, modified VV Ankara (MVA). By live-cell imaging, small, early replication sites of both viruses undergo motility typical of microtubule (MT)-motor-mediated movement. Over time, growing replication sites of VV collect around the nucleus in a MT-dependent fashion, whereas those of MVA remain mostly scattered in the cytoplasm. Surprisingly, blocking the dynein function does not impair the perinuclear accumulation of large VV replication sites. Live-cell imaging demonstrates that in contrast to small replication sites, large sites do not display MT-motor-mediated motility. Instead, VV infection induces cellular contractility that facilitates the collection of growing replication sites around the nucleus. In a subset of cells (30-40%), this VV-induced contractility is alternated by phases of directed cell migration, suggesting that the two processes may be linked. The MVA-infected cells do not display contractility or cell migration, supporting the idea that these cellular activities facilitate the efficient accumulation of the VV replication sites around the nucleus. We propose that the recently described cytoskeletal rearrangements induced by VV are a prerequisite for the observed cell contractility and migration activities that apparently contribute to the organization of the complex cytoplasmic life cycle of VV.
authors.affiliation: EMBL, Cell Biology and Biophysics Programme, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Schramm
authors.forename: Cornelis A M
authors.initials: CA
authors.lastname: de Haan
authors.forename: Joanne
authors.initials: J
authors.lastname: Young
authors.forename: Laura
authors.initials: L
authors.lastname: Doglio
authors.forename: Sibylle
authors.initials: S
authors.lastname: Schleich
authors.forename: Christoph
authors.initials: C
authors.lastname: Reese
authors.forename: Andrei V
authors.initials: AV
authors.lastname: Popov
authors.forename: Walter
authors.initials: W
authors.lastname: Steffen
authors.forename: Trina
authors.initials: T
authors.lastname: Schroer
authors.forename: Jacomine Krijnse
authors.initials: JK
authors.lastname: Locker
mesh_terms: D000818:Animals; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D002467:Cell Nucleus / Q000821:virology*; D003593:Cytoplasm / Q000821:virology*; D000072159:Dynactin Complex; D004398:Dyneins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D018715:Microscopy, Video; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism; D020409:Molecular Motor Proteins / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D014616:Vaccinia virus / Q000502:physiology*; D014779:Virus Replication
chemical_list: D000072159:Dynactin Complex; D008869:Microtubule-Associated Proteins; D020409:Molecular Motor Proteins; D034741:RNA, Small Interfering; D004398:Dyneins