Deerpox virus encodes an inhibitor of apoptosis that regulates Bak and Bax

J Virol. 2011 Mar;85(5):1922-34. doi: 10.1128/JVI.01959-10. Epub 2010 Dec 15.


Poxviruses encode numerous proteins that inhibit apoptosis, a form of cell death critical to the elimination of virally infected cells. Sequencing of the deerpox virus genome revealed DPV022, a protein that lacks obvious homology to cellular members of the Bcl-2 family but shares limited regions of amino acid identity with two unique poxviral inhibitors of apoptosis, M11L and F1L. Given the limited homology, we sought to determine whether DPV022 could inhibit apoptosis. Here we show that DPV022 localized to the mitochondria, where it inhibited apoptosis. We used a Saccharomyces cerevisiae model system to demonstrate that in the absence of all other Bcl-2 family proteins, DPV022 interacted directly with Bak and Bax. We confirmed the ability of DPV022 to interact with Bak and Bax by immunoprecipitation and showed that DPV022 prevented apoptosis induced by Bak and Bax overexpression. Moreover, we showed that DPV022 blocked apoptosis even when all the endogenous mammalian antiapoptotic proteins were neutralized by a combination of selective BH3 ligands. During virus infection, DPV022 interacted with endogenous Bak and Bax and prevented the conformational activation of both of them. Thus, we have characterized a novel poxviral inhibitor of apoptosis with intriguing amino acid differences from the well-studied proteins M11L and F1L.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Apoptosis*
  • Cell Line
  • Down-Regulation
  • Humans
  • Mitochondria / metabolism
  • Mitochondria / virology
  • Molecular Sequence Data
  • Poxviridae / genetics
  • Poxviridae / metabolism*
  • Poxviridae Infections / genetics
  • Poxviridae Infections / metabolism*
  • Poxviridae Infections / physiopathology
  • Poxviridae Infections / virology
  • Protein Binding
  • Protein Transport
  • Sequence Alignment
  • Viral Proteins / chemistry
  • Viral Proteins / genetics
  • Viral Proteins / metabolism*
  • bcl-2 Homologous Antagonist-Killer Protein / chemistry
  • bcl-2 Homologous Antagonist-Killer Protein / genetics
  • bcl-2 Homologous Antagonist-Killer Protein / metabolism*
  • bcl-2-Associated X Protein / chemistry
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism*


  • Viral Proteins
  • bcl-2 Homologous Antagonist-Killer Protein
  • bcl-2-Associated X Protein