Identification of unusual E6 and E7 proteins within avian papillomaviruses: cellular localization, biophysical characterization, and phylogenetic analysis.
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.
Van Doorslaer
Koenraad
K
Laboratory of Clinical Virology, Rega Institute for Medical Research, University of Leuven, Minderbroedersstraat 10, 3000 Leuven, Belgium.
Sidi
Abdellahi Ould M'hamed  Ould
AO
Zanier
Katia
K
Rybin
Vladimir
V
Deryckère
François
F
Rector
Annabel
A
Burk
Robert D
RD
Lienau
E Kurt
EK
van Ranst
Marc
M
Travé
Gilles
G
D000595:Amino Acid Sequence; D000818:Animals; D001715:Bird Diseases / Q000821:virology*; D001717:Birds; D002467:Cell Nucleus / Q000737:chemistry; D016000:Cluster Analysis; D003593:Cytoplasm / Q000737:chemistry; D004279:DNA, Viral / Q000737:chemistry / Q000235:genetics; D019143:Evolution, Molecular; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009856:Oncogene Proteins, Viral / Q000032:analysis / Q000737:chemistry* / Q000235:genetics*; D027383:Papillomaviridae / Q000235:genetics* / Q000302:isolation & purification; D030361:Papillomavirus Infections / Q000662:veterinary*; D010802:Phylogeny; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017385:Sequence Homology
D004279:DNA, Viral; D009856:Oncogene Proteins, Viral