Key result
Inactivation of endogenous gelsolin blocked the release of infectious parvovirus virions into the culture medium, leading to a 30-fold reduction in medium-associated titers.
Effect estimate: 30-fold reduction
Gelsolin-dependent actin degradation is essential for the vesicular egress of non-enveloped lytic parvoviruses, challenging the view that their egress is purely a passive process.
Challenges passive lysis model for parvovirus egress; leaves open gelsolin as potential antiviral target pending in vivo validation.
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.
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Bär et al. (2008) studied Parvovirus infection (in vitro). Gelsolin inactivation (neutralizing antibodies or dominant-negative mutants) vs. Control serum/IgG or wild-type cells was evaluated on Release of infectious virions into the culture medium (30-fold reduction). Inactivation of endogenous gelsolin blocked the release of infectious parvovirus virions into the culture medium, leading to a 30-fold reduction in medium-associated titers.
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