The E1 proteins

Virology. 2013 Oct;445(1-2):35-56. doi: 10.1016/j.virol.2013.07.020. Epub 2013 Sep 10.


E1, an ATP-dependent DNA helicase, is the only enzyme encoded by papillomaviruses (PVs). It is essential for replication and amplification of the viral episome in the nucleus of infected cells. To do so, E1 assembles into a double-hexamer at the viral origin, unwinds DNA at the origin and ahead of the replication fork and interacts with cellular DNA replication factors. Biochemical and structural studies have revealed the assembly pathway of E1 at the origin and how the enzyme unwinds DNA using a spiral escalator mechanism. E1 is tightly regulated in vivo, in particular by post-translational modifications that restrict its accumulation in the nucleus. Here we review how different functional domains of E1 orchestrate viral DNA replication, with an emphasis on their interactions with substrate DNA, host DNA replication factors and modifying enzymes. These studies have made E1 one of the best characterized helicases and provided unique insights on how PVs usurp different host-cell machineries to replicate and amplify their genome in a tightly controlled manner.

Keywords: ATPase; DNA replication; E1; Episome; Helicase; Papillomavirus; Phosphoryaltion; Post-translational modifications.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cell Nucleus / virology
  • DNA Helicases / genetics
  • DNA Helicases / metabolism*
  • DNA Replication*
  • DNA, Viral / genetics
  • Enzyme Activation
  • Genome, Viral*
  • Humans
  • Oncogene Proteins, Viral / genetics
  • Oncogene Proteins, Viral / metabolism*
  • Papillomaviridae / enzymology*
  • Papillomaviridae / genetics
  • Papillomaviridae / physiology
  • Protein Multimerization
  • Protein Processing, Post-Translational
  • Protein Structure, Tertiary
  • Virus Replication*


  • DNA, Viral
  • Oncogene Proteins, Viral
  • oncogene protein E1, Human papillomavirus type 18
  • DNA Helicases