Vesicular egress of non-enveloped lytic parvoviruses depends on gelsolin functioning.
The autonomous parvovirus Minute Virus of Mice (MVM) induces specific changes in the cytoskeleton filaments of infected permissive cells, causing in particular the degradation of actin fibers and the generation of "actin patches." This is attributed to a virus-induced imbalance between the polymerization factor N-WASP (Wiscott-Aldrich syndrome protein) and gelsolin, a multifunctional protein cleaving actin filaments. Here, the focus is on the involvement of gelsolin in parvovirus propagation and virus-induced actin processing. Gelsolin activity was knocked-down, and consequences thereof were determined for virus replication and egress and for actin network integrity. Though not required for virus replication or progeny particle assembly, gelsolin was found to control MVM (and related H1-PV) transport from the nucleus to the cell periphery and release into the culture medium. Gelsolin-dependent actin degradation and progeny virus release were both controlled by (NS1)/CKIIalpha, a recently identified complex between a cellular protein kinase and a MVM non-structural protein. Furthermore, the export of newly synthesized virions through the cytoplasm appeared to be mediated by (virus-modified) lysomal/late endosomal vesicles. By showing that MVM release, like entry, is guided by the cytoskeleton and mediated by vesicles, these results challenge the current view that egress of non-enveloped lytic viruses is a passive process.
Bär
Séverine
S
Program Infection and Cancer, Abteilung F010 and Institut National de la Santé et de la Recherche Médicale U701, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
Daeffler
Laurent
L
Rommelaere
Jean
J
Nüesch
Jürg P F
JP
D008841:Actin Cytoskeleton / Q000378:metabolism; D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000818:Animals; D047390:Casein Kinase II / Q000378:metabolism; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism* / Q000821:virology; D011992:Endosomes / Q000378:metabolism / Q000821:virology; D018260:Gelsolin / Q000378:metabolism*; D006801:Humans; D008247:Lysosomes / Q000378:metabolism / Q000821:virology; D008915:Minute Virus of Mice / Q000502:physiology*; D010322:Parvoviridae Infections / Q000378:metabolism; D017361:Viral Nonstructural Proteins; D014771:Virion / Q000378:metabolism; D014779:Virus Replication / Q000502:physiology*; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal / Q000378:metabolism
D018260:Gelsolin; D017361:Viral Nonstructural Proteins; C495771:WASL protein, human; C495772:Wasl protein, mouse; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal; D047390:Casein Kinase II