Merkel cell polyomavirus large T antigen has growth-promoting and inhibitory activities

J Virol. 2013 Jun;87(11):6118-26. doi: 10.1128/JVI.00385-13. Epub 2013 Mar 20.


Merkel cell carcinoma (MCC) is a rare and aggressive form of skin cancer. In at least 80% of all MCC, Merkel cell polyomavirus (MCPyV) DNA has undergone clonal integration into the host cell genome, and most tumors express the MCPyV large and small T antigens. In all cases of MCC reported to date, the integrated MCPyV genome has undergone mutations in the large T antigen. These mutations result in expression of a truncated large T antigen that retains the Rb binding or LXCXE motif but deletes the DNA binding and helicase domains. However, the transforming functions of full-length and truncated MCPyV large T antigen are unknown. We compared the transforming activities of full-length, truncated, and alternatively spliced 57kT forms of MCPyV large T antigen. MCPyV large T antigen could bind to Rb but was unable to bind to p53. Furthermore, MCPyV-truncated large T antigen was more effective than full-length and 57kT large T antigen in promoting the growth of human and mouse fibroblasts. In contrast, expression of the MCPyV large T antigen C-terminal 100 residues could inhibit the growth of several different cell types. These data imply that the deletion of the C terminus of MCPyV large T antigen found in MCC serves not only to disrupt viral replication but also results in the loss of a distinct growth-inhibitory function intrinsic to this region.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Motifs
  • Animals
  • Antigens, Polyomavirus Transforming / chemistry
  • Antigens, Polyomavirus Transforming / genetics
  • Antigens, Polyomavirus Transforming / metabolism*
  • Carcinoma, Merkel Cell / genetics
  • Carcinoma, Merkel Cell / metabolism
  • Carcinoma, Merkel Cell / physiopathology*
  • Carcinoma, Merkel Cell / virology
  • Cell Proliferation
  • Cell Transformation, Neoplastic
  • Growth Substances / chemistry
  • Growth Substances / genetics
  • Growth Substances / metabolism*
  • Humans
  • Merkel cell polyomavirus / chemistry
  • Merkel cell polyomavirus / genetics
  • Merkel cell polyomavirus / physiology*
  • Mice
  • Skin Neoplasms / genetics
  • Skin Neoplasms / metabolism
  • Skin Neoplasms / physiopathology*
  • Skin Neoplasms / virology
  • Tumor Virus Infections / genetics
  • Tumor Virus Infections / metabolism
  • Tumor Virus Infections / physiopathology*
  • Tumor Virus Infections / virology


  • Antigens, Polyomavirus Transforming
  • Growth Substances