vesicular egress of non-enveloped lytic parvoviruses depends on gelsolin functioning水泡出口无包膜的裂解细小病毒取决于gelsolin功能.pdfVIP

Vesicular Egress of Non-Enveloped Lytic Parvoviruses Depends on Gelsolin Functioning ´ ¨ ¨ ¨ Severine Bar, Laurent Daeffler, Jean Rommelaere, Jurg P. F. Nuesch* ´ ´ Program ‘‘Infection and Cancer,’’ Abteilung F010 and Institut National de la Sante et de la Recherche Medicale U701, Deutsches Krebsforschungszentrum, Heidelberg, Germany Abstract 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)/CKIIa, 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