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Structural and Functional Insight into Canarypox Virus CNP058 Mediated Regulation of Apoptosis

Mohd Ishtiaq Anasir1, Amy A Baxter2, Ivan K H Poon3

  • 1Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086, Australia. 17818130@students.latrobe.edu.au.

Viruses
|October 21, 2017
PubMed

Insights

Canarypox virus protein CNP058 inhibits programmed cell death (apoptosis) by binding to host cell proteins. This viral mimicry counters host defenses, potentially aiding viral replication by preventing premature cell death.

Area of Science:

  • Virology
  • Molecular Biology
  • Cell Biology

Background:

  • Programmed cell death (apoptosis) is crucial for host defense against viral infections.
  • Viruses often encode proteins that mimic host anti-apoptotic factors to evade immune responses.
  • The canarypox virus protein CNP058 was identified as a potential viral anti-apoptotic factor.

Purpose of the Study:

  • To investigate the role of canarypox virus protein CNP058 in apoptosis inhibition.
  • To characterize the binding interactions of CNP058 with host cell death regulators.
  • To determine the structural basis of CNP058's interaction with pro-death Bcl-2 proteins.

Main Methods:

  • Protein binding assays to assess CNP058 interactions with various pro-death Bcl-2 family members and BH3-only proteins.
  • Crystal structure determination of CNP058 complexed with Bim BH3 peptide.
  • Cell-based assays to evaluate CNP058's effect on UV-induced apoptosis.

Main Results:

  • CNP058 binds with high to moderate affinity to multiple host pro-death Bcl-2 proteins (Bak, Bax) and BH3-only proteins (Bim, Bid, Bmf, Noxa, Puma, Hrk).
  • The crystal structure reveals CNP058 adopts a Bcl-2-like fold and binds Bim BH3 in a conserved groove.
  • CNP058 effectively inhibits ultraviolet (UV) radiation-induced apoptosis in cell culture.

Conclusions:

  • CNP058 is a potent inhibitor of apoptosis, acting as a viral mimic of cellular pro-survival Bcl-2 proteins.
  • Its broad binding to pro-death Bcl-2 proteins suggests a significant role in subverting host apoptosis during infection.
  • CNP058 represents a key viral strategy to counteract premature host cell death and promote viral propagation.
Keywords:
Bcl-2X-ray crystallographyapoptosisavipoxvirusisothermal titration calorimetrypoxvirus

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