Higher detection of JC polyomavirus in colorectal cancerous tissue after pretreatment with topoisomerase I enzyme; colorectal tissue serves as a JCPyV persistence site

Exp Mol Pathol. 2021 Dec:123:104687. doi: 10.1016/j.yexmp.2021.104687. Epub 2021 Sep 27.

Abstract

Background: The JC polyomavirus has been blamed to contribute in colorectal cancer (CRC), however, the topic is still controversial. Varying detection rate of JCPyV genome has been reported mainly due to technical reasons. Here, we provide summative data on the topic, with emphasize on technical issues.

Methods: Formalin-fixed paraffin-embedded tissue samples from 50 patients with CRC, consisting of tumoral and non-cancerous marginal tissue (totally 100 samples) were included in the study. After DNA extraction, specific JCPyV T-Ag sequences were targeted using Real-time PCR. To unwind the supercoiled JCPyV genome, pretreatment with topoisomerase I, was applied. Immunohistochemical (IHC) staining was performed using an anti-T-Ag monoclonal antibody.

Results: In the first attempts, no samples were found to be positive in Real-time PCR assays. However, JCPyV sequences were found in 60% of CRC tissues and 38% of non-cancerous colorectal mucosa after application of pre-treatment step with topoisomerase I enzyme (P = 0.028). T-Ag protein was found in the nuclear compartment of the stained cells in IHC assays.

Conclusions: The presence of JCPyV in CRC tissues, as well as T-Ag localization in the nucleolus, where its oncogenic effect takes place, may provide supporting evidence for JCPyV involvement in CRC development. The study highlights the importance of using topoisomerase I to enhance JCPyV genome detection. Also, colorectal tissue is one of the permissive human tissue for JC resistance after preliminary infection.

Keywords: Colorectal neoplasm; JC virus; Large T-antigen; Topoisomerase I.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Nucleolus / genetics
  • Cell Nucleolus / virology
  • Colorectal Neoplasms / complications
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / virology*
  • DNA Topoisomerases, Type I / chemistry
  • DNA Topoisomerases, Type I / pharmacology*
  • Female
  • Genome, Viral / genetics*
  • Humans
  • JC Virus / genetics
  • JC Virus / isolation & purification*
  • JC Virus / pathogenicity
  • Male
  • Middle Aged
  • Polyomavirus Infections / complications
  • Polyomavirus Infections / genetics
  • Polyomavirus Infections / pathology
  • Polyomavirus Infections / virology
  • Virus Replication / genetics

Substances

  • DNA Topoisomerases, Type I