Identification of unusual E6 and E7 proteins within avian papillomaviruses: cellular localization, biophysical characterization, and phylogenetic analysis

J Virol. 2009 Sep;83(17):8759-70. doi: 10.1128/JVI.01777-08. Epub 2009 Jun 24.

Abstract

Papillomaviruses (PVs) are a large family of small DNA viruses infecting mammals, reptiles, and birds. PV infection induces cell proliferation that may lead to the formation of orogenital or skin tumors. PV-induced cell proliferation has been related mainly to the expression of two small oncoproteins, E6 and E7. In mammalian PVs, E6 contains two 70-residue zinc-binding repeats, whereas E7 consists of a natively unfolded N-terminal region followed by a zinc-binding domain which folds as an obligate homodimer. Here, we show that both the novel francolin bird PV Francolinus leucoscepus PV type 1 (FlPV-1) and the chaffinch bird PV Fringilla coelebs PV contain unusual E6 and E7 proteins. The avian E7 proteins contain an extended unfolded N terminus and a zinc-binding domain of reduced size, whereas the avian E6 proteins consist of a single zinc-binding domain. A comparable single-domain E6 protein may have existed in a common ancestor of mammalian and avian PVs. Mammalian E6 C-terminal domains are phylogenetically related to those of single-domain avian E6, whereas mammalian E6 N-terminal domains seem to have emerged by duplication and subsequently diverged from the original ancestral domain. In avian and mammalian cells, both FlPV-1 E6 and FlPV-1 E7 were evenly expressed in the cytoplasm and the nucleus. Finally, samples of full-length FlPV-1 E6 and the FlPV-1 E7 C-terminal zinc-binding domain were prepared for biophysical analysis. Both constructs were highly soluble and well folded, according to nuclear magnetic resonance spectroscopy measurements.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Bird Diseases / virology*
  • Birds
  • Cell Nucleus / chemistry
  • Cluster Analysis
  • Cytoplasm / chemistry
  • DNA, Viral / chemistry
  • DNA, Viral / genetics
  • Evolution, Molecular
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Molecular Sequence Data
  • Oncogene Proteins, Viral / analysis
  • Oncogene Proteins, Viral / chemistry*
  • Oncogene Proteins, Viral / genetics*
  • Papillomaviridae / genetics*
  • Papillomaviridae / isolation & purification
  • Papillomavirus Infections / veterinary*
  • Phylogeny
  • Protein Folding
  • Protein Structure, Tertiary
  • Sequence Alignment
  • Sequence Analysis, DNA
  • Sequence Homology

Substances

  • DNA, Viral
  • Oncogene Proteins, Viral

Associated data

  • GENBANK/EU188799