Cellular factors required for papillomavirus DNA replication

J Virol. 1995 Dec;69(12):7857-67. doi: 10.1128/JVI.69.12.7857-7867.1995.


In vitro replication of papillomavirus DNA has been carried out with a combination of purified proteins and partially purified extracts made from human cells. DNA synthesis requires the viral E1 protein and the papillomavirus origin of replication. The E2 protein stimulates DNA synthesis in a binding site-independent manner. Papillomavirus DNA replication is also dependent on the cellular factors replication protein A, replication factor C, and proliferating-cell nuclear antigen as well as a phosphocellulose column fraction (IIA). Fraction IIA contains DNA polymerase alpha-primase and DNA polymerase delta. Both of these polymerases are essential for papillomavirus DNA replication in vitro. However, unlike the case with T-antigen-dependent replication from the simian virus 40 origin, purified DNA polymerase alpha-primase and delta cannot efficiently replace fraction IIA in the replication reaction. Hence, additional cellular factors seem to be required for papillomavirus DNA replication. Interestingly, replication factor C and proliferating-cell nuclear antigen are more stringently required for DNA synthesis in the papillomavirus system than in the simian virus 40 in vitro system. These distinctions indicate that there must be mechanistic differences between the DNA replication systems of papillomavirus and simian virus 40.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Bovine papillomavirus 1 / genetics
  • Bovine papillomavirus 1 / metabolism
  • Cell-Free System
  • DNA Polymerase III
  • DNA Primase
  • DNA Replication*
  • DNA, Viral / biosynthesis*
  • DNA-Binding Proteins / metabolism
  • DNA-Directed DNA Polymerase / metabolism
  • Homeodomain Proteins*
  • Humans
  • Kinetics
  • Minor Histocompatibility Antigens
  • Oncogene Proteins, Viral / metabolism
  • Papillomaviridae / genetics*
  • Papillomaviridae / metabolism
  • Plasmids
  • Proliferating Cell Nuclear Antigen / metabolism
  • Proto-Oncogene Proteins c-bcl-2*
  • RNA Nucleotidyltransferases / metabolism
  • Replication Protein A
  • Replication Protein C
  • Repressor Proteins*
  • Saccharomyces cerevisiae Proteins*
  • Simian virus 40 / genetics
  • Species Specificity


  • BCL2-related protein A1
  • DNA, Viral
  • DNA-Binding Proteins
  • Homeodomain Proteins
  • MATA1 protein, S cerevisiae
  • Minor Histocompatibility Antigens
  • Oncogene Proteins, Viral
  • Proliferating Cell Nuclear Antigen
  • Proto-Oncogene Proteins c-bcl-2
  • RPA1 protein, human
  • Replication Protein A
  • Repressor Proteins
  • Saccharomyces cerevisiae Proteins
  • DNA Primase
  • RNA Nucleotidyltransferases
  • DNA Polymerase III
  • DNA-Directed DNA Polymerase
  • Replication Protein C