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A viral adaptor protein modulating casein kinase II activity induces cytopathic effects in permissive cells

Jürg P F Nüesch1, Jean Rommelaere

  • 1Program "Infection and Cancer," Abteilung F010 and Institut National de la Santé et de la Recherche Médicale Unité 701, Deutsches Krebsforschungszentrum, D-69120 Heidelberg, Germany. jpf.nuesch@dkfz.de

Proceedings of the National Academy of Sciences of the United States of America
|July 20, 2007
PubMed

Insights

The parvovirus NS1 protein causes cell damage by linking casein kinase II (CKII) to tropomyosin, altering cell structures. This NS1 adaptor function is crucial for parvovirus-induced cell death and cytoskeletal changes.

Area of Science:

  • Virology
  • Cell Biology
  • Biochemistry

Background:

  • Autonomous parvoviruses cause significant cell damage (cytopathic effects, CPE) through cytoskeletal disruption.
  • Casein kinase II (CKII) inhibition protects cells from Minute virus of mice (MVM)-induced CPE, suggesting its role in MVM toxicity.

Purpose of the Study:

  • To investigate the role of the parvoviral NS1 protein in mediating CKII-dependent cytoskeletal alterations and cell death.
  • To elucidate the mechanism by which NS1 induces CPE.

Main Methods:

  • Investigated the interaction between NS1, CKIIalpha, and tropomyosin using in vitro and in vivo assays.
  • Analyzed the effect of NS1 mutations on binding affinities and CPE induction.
  • Utilized fusion peptides to confirm the adaptor function of NS1.

Main Results:

  • The parvoviral NS1 protein directly mediates CKII-dependent cytoskeletal alterations and cell death.
  • NS1 acts as an adaptor, linking CKIIalpha to tropomyosin, altering tropomyosin phosphorylation.
  • Mutations in NS1 that disrupt binding to CKIIalpha or tropomyosin impair its ability to induce CPE.
  • Fusion peptides mimicking NS1's adaptor function induced cell death in MVM-permissive cells.

Conclusions:

  • The NS1 protein's cytotoxic adaptor function, linking CKIIalpha and tropomyosin, is essential for inducing parvovirus-mediated cell death.
  • NS1's ability to modulate tropomyosin phosphorylation via CKII is a key mechanism driving parvoviral CPE.

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