HPV-18 E2^E4 chimera: 2 new spliced transcripts and proteins induced by keratinocyte differentiation

Virology. 2012 Jul 20;429(1):47-56. doi: 10.1016/j.virol.2012.03.023. Epub 2012 Apr 27.


The Human Papillomavirus (HPV) E4 is known to be synthesized as an E1^E4 fusion resulting from splice donor and acceptor sites conserved across HPV types. Here we demonstrate the existence of 2 HPV-18 E2^E4 transcripts resulting from 2 splice donor sites in the 5' part of E2, while the splice acceptor site is the one used for E1^E4. Both E2^E4 transcripts are up-regulated by keratinocyte differentiation in vitro and can be detected in clinical samples containing low-grade HPV-18-positive cells from Pap smears. They give rise to two fusion proteins in vitro, E2^E4-S and E2^E4-L. Whereas we could not differentiate E2^E4-S from E1^E4 in vivo, E2^E4-L could be formally identified as a 23 kDa protein in raft cultures in which the corresponding transcript was also found, and in a biopsy from a patient with cervical intraepithelial neoplasia stage I-II (CINI-II) associated with HPV-18, demonstrating the physiological relevance of E2^E4 products.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Cell Differentiation*
  • Female
  • Human papillomavirus 18 / genetics
  • Human papillomavirus 18 / metabolism*
  • Humans
  • Keratinocytes / cytology*
  • Keratinocytes / virology
  • Molecular Sequence Data
  • Oncogene Proteins, Viral / genetics
  • Oncogene Proteins, Viral / metabolism*
  • Papillomavirus Infections / physiopathology
  • Papillomavirus Infections / virology*
  • RNA Splice Sites
  • RNA Splicing*
  • RNA, Viral / genetics
  • RNA, Viral / metabolism


  • Oncogene Proteins, Viral
  • RNA Splice Sites
  • RNA, Viral
  • oncogene protein E2, Human papillomavirus type 18
  • oncogene protein E4, Human papillomavirus type 18