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Transformed cell-specific induction of apoptosis by porcine circovirus type 1 viral protein 3

Kenneth P Hough1, Andrew M Rogers1, Matija Zelic1

  • 1Department of Chemistry and Biochemistry, Worcester Polytechnic Institute, 100 Institute Road, Worcester, MA 01609, USA.

The Journal of General Virology
|November 9, 2014
PubMed

Insights

Porcine circovirus type 1 (PCV1) encodes a viral protein (VP3) that induces apoptosis selectively in transformed cells, similar to chicken anemia virus (CAV) apoptin. However, PCV1 VP3 causes G1 cell cycle arrest, unlike CAV apoptin's G2/M arrest.

Area of Science:

  • Virology
  • Molecular Biology
  • Cell Biology

Background:

  • Circoviridae family viruses, including porcine circovirus type 2 (PCV2) and chicken anemia virus (CAV), encode cytotoxic viral proteins (VP3) that induce apoptosis.
  • CAV's VP3, apoptin, induces apoptosis specifically in transformed cells.
  • Genomic similarities suggest PCV type 1 (PCV1) may also encode a VP3 with similar apoptotic activity.

Purpose of the Study:

  • To investigate the presence and function of a putative ORF3 in PCV1, homologous to CAV and PCV2 VP3.
  • To characterize the PCV1 VP3 protein, its localization, and its apoptotic activity.

Main Methods:

  • Open reading frame (ORF) prediction and gene expression analysis.
  • Sequence analysis to identify functional domains and signals.
  • Subcellular localization studies.
  • Cytotoxicity assays and cell cycle analysis.

Main Results:

  • A putative ORF3 was identified in PCV1, encoding a viral protein (PCV1 VP3) functionally similar to apoptin and PCV2 VP3.
  • PCV1 VP3 possesses a unique hydrophobic C-terminal domain with a nuclear export signal, leading to distinct subcellular localization compared to CAV VP3.
  • PCV1 VP3 induces apoptosis selectively in transformed cells, similar to apoptin, but causes a G1 cell cycle arrest instead of the G2/M arrest observed with apoptin.
  • Nuclear localization is not essential for PCV1 VP3-induced apoptosis or transformed cell selectivity.

Conclusions:

  • PCV1 encodes a VP3 protein with apoptotic activity and transformed cell selectivity.
  • PCV1 VP3 exhibits a distinct mechanism of action compared to CAV apoptin, characterized by G1 cell cycle arrest and unique localization patterns.
  • These findings highlight functional divergence within the VP3 proteins of the Circoviridae family.

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