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Updated: May 7, 2026

Merkel Cell Polyomavirus Infection and Detection
13:45

Merkel Cell Polyomavirus Infection and Detection

Published on: February 7, 2019

The T antigen locus of Merkel cell polyomavirus downregulates human Toll-like receptor 9 expression

Naveed Shahzad1, Masahiro Shuda, Tarik Gheit

  • 1International Agency for Research on Cancer, Lyon, France.

Journal of Virology
|September 27, 2013
PubMed

Insights

Merkel cell polyomavirus (MCPyV) oncoproteins downregulate Toll-like receptor 9 (TLR9) expression, a key immune sensor. This viral immune evasion mechanism may contribute to MCPyV-driven Merkel cell carcinoma development.

Area of Science:

  • Virology
  • Immunology
  • Oncology

Background:

  • Chronic viral infections are linked to cancer development.
  • Cancer-associated viruses often evade the immune system by downregulating Toll-like receptor 9 (TLR9), which detects viral DNA.
  • Merkel cell polyomavirus (MCPyV) is a novel oncogenic virus causing Merkel cell carcinoma (MCC), but its immune evasion strategies are unclear.

Purpose of the Study:

  • To investigate whether MCPyV disrupts immune-related pathways, specifically TLR9 expression.
  • To elucidate the mechanism by which MCPyV may affect TLR9 expression.
  • To compare the effects of MCPyV with other polyomaviruses on TLR9 expression.

Main Methods:

  • Studied the effect of MCPyV large T antigen (LT) and small T antigen (sT) expression on TLR9 levels in epithelial and MCC cells.
  • Utilized gene silencing to assess the impact of LT and sT on TLR9 mRNA.
  • Investigated the role of the C/EBPβ transactivator in MCPyV-mediated TLR9 downregulation using promoter analysis and chromatin immunoprecipitation.
  • Surveyed multiple polyomaviruses for their ability to inhibit TLR9 gene expression.

Main Results:

  • MCPyV LT and sT expression significantly downregulate TLR9 expression in relevant cell types.
  • Silencing LT or sT leads to increased TLR9 mRNA levels.
  • MCPyV LT inhibits TLR9 by reducing C/EBPβ mRNA levels, a positive regulator of the TLR9 promoter.
  • MCPyV early gene expression inhibits C/EBPβ binding to the TLR9 promoter, and mutation of this site prevents MCPyV-induced TLR9 downregulation.
  • Only MCPyV and BK polyomavirus (BKPyV) among the tested viruses potently inhibit TLR9 expression.

Conclusions:

  • MCPyV oncoproteins, particularly LT, actively downregulate TLR9 expression.
  • This downregulation is mediated by inhibiting the C/EBPβ transactivator, crucial for TLR9 promoter activity.
  • MCPyV's targeting of TLR9 likely contributes to viral persistence and immune evasion, facilitating tumorigenesis in MCC.

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