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The coxsackievirus 2B protein suppresses apoptotic host cell responses by manipulating intracellular Ca2+ homeostasis

Michelangelo Campanella1, Arjan S de Jong, Kjerstin W H Lanke

  • 1Department of Experimental and Diagnostic Medicine, Section of General Pathology and Center for the Study of Inflammatory Diseases, Via Borsari 46, I-44100 Ferrara, Italy.

The Journal of Biological Chemistry
|February 21, 2004
PubMed

Insights

Enteroviruses prevent cell death by altering calcium (Ca2+) levels. The coxsackievirus 2B protein disrupts intracellular Ca2+ stores, suppressing apoptosis and aiding viral survival.

Area of Science:

  • Virology
  • Cell Biology
  • Biochemistry

Background:

  • Enteroviruses are RNA viruses that induce an antiapoptotic state in host cells.
  • This viral strategy suppresses apoptosis, which limits viral infection.
  • The specific viral protein and mechanism responsible for this antiapoptotic effect remain unidentified.

Purpose of the Study:

  • To identify the enteroviral protein responsible for modulating apoptosis.
  • To elucidate the mechanism by which enteroviruses suppress host cell apoptosis.
  • To investigate the role of intracellular calcium (Ca2+) homeostasis in enteroviral antiapoptotic strategies.

Main Methods:

  • Ectopic expression of coxsackievirus 2B protein in HeLa cells.
  • Utilized fluorescent Ca2+ indicators and organelle-targeted aequorins to measure intracellular Ca2+ levels.
  • Assessed caspase activation and apoptotic cell death induced by actinomycin D and cycloheximide.
  • Generated and analyzed 2B mutants defective in Ca2+ store content reduction.

Main Results:

  • Ectopic expression of coxsackievirus 2B protein decreased Ca2+ content in the endoplasmic reticulum and Golgi.
  • 2B expression down-regulated Ca2+ signaling between organelles and mitochondria, increasing extracellular Ca2+ influx.
  • 2B expression suppressed caspase activation and apoptosis induced by metabolic inhibitors.
  • 2B mutants unable to reduce Ca2+ store content failed to suppress apoptosis.

Conclusions:

  • The coxsackievirus 2B protein manipulates intracellular Ca2+ homeostasis to suppress apoptosis.
  • Perturbation of intracellular Ca2+ compartmentalization is crucial for enteroviral evasion of host apoptotic responses.
  • This study implicates a novel mechanism involving Ca2+ dysregulation in viral pathogenesis.

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