Human Gyrovirus-Apoptin Interferes with the Cell Cycle and Induces G2/M Arrest Prior to Apoptosis

Arch Immunol Ther Exp (Warsz). 2017 Dec;65(6):545-552. doi: 10.1007/s00005-017-0464-8. Epub 2017 Apr 6.

Abstract

The human gyrovirus-Apoptin (HGyv-Apoptin) is a protein that gained attention because it is selectively cytotoxic toward cancer cells. In this study, we have investigated the effect of HGyv-Apoptin on cell cycle progression of cancer cells. We also compared HGyv-Apoptin's action to its homologue chicken anemia virus Apoptin (CAV-Apoptin). We show that HGyv-Apoptin induces G2/M arrest in cancer cells. This is at least in part due to the fact that HGyv-Apoptin induces an abnormal spindle formation in mitotic cells that do not progress properly throughout the cell cycle. HGyv-Apoptin most likely inhibits APC function leading to a sustained cyclin-B1-expression. These results indicate that HGyv-Apoptin has a similar mechanism of action as its homolog CAV-Apoptin and further supports its cancer therapeutic potential.

Keywords: APC; Apoptin; Cell cycle; Cyclin B1; PKTCs.

MeSH terms

  • Anaphase-Promoting Complex-Cyclosome / metabolism
  • Animals
  • Capsid Proteins / genetics
  • Capsid Proteins / metabolism*
  • Cell Cycle*
  • Chicken anemia virus / immunology*
  • Circoviridae Infections / metabolism*
  • Cyclin B1 / genetics
  • Cyclin B1 / metabolism
  • G2 Phase Cell Cycle Checkpoints
  • Gyrovirus / immunology*
  • HCT116 Cells
  • Humans

Substances

  • Capsid Proteins
  • Cyclin B1
  • VP3 protein, Chicken anemia virus
  • Anaphase-Promoting Complex-Cyclosome