The E10 ORF

The E10 ORF was named in July 2016, based on suggestions from senior members of the papillomavirus community at the DNA Tumor Virus Conference in Montreal. E10 is now designated as an ORF that either overprints the E6 ORF, or is encoded in this region (in the absence of an E6 gene) in certain papillomaviruses. At this point, E10 ORFs are only annotated in PaVE for Xi and Kappa papillomaviruses, since there is published evidence for the function of these proteins in these viruses.

Historical Designation

Proteins predicted to be encoded by the ORFs that overprint E6 are very hydrophobic and this has previously sometimes led to their designation as E5 (1). This has led to confusion because the traditional E5 protein is encoded in the 3’ end of the early coding region. In some viruses, similar proteins have also been named E8 (2). However, the term E8 is now widely used to describe the small 5’ exon that overprints the E1 ORF, and encodes the E8^E2 protein (3). The official designation of these transcripts as E8^E2 was also ratified by senior members of the papillomavirus community in 2016 (3).

Examples of E10 Proteins

Xipapillomavirus E10

ORFs that encode hydrophobic proteins are located in the E6 position of the bovine Xipapillomaviruses. These were were originally designated E8 (4-6), and later changed to E5 (1). These have now been renamed E10 in the PaVE database. There is evidence that BPV4 E10 (formerly E8/E5) is important for cellular transformation (1, 6, 7).


SfPV1 contains a hydrophobic ORF within E6 that is similar to the HPV and BPV1 E5 proteins, and was originally designated E8 (8). There is substantial evidence that SfPV1 E10 (formerly E8) is involved in cellular transformation and wart formation (7-11) and can induce protective immunity against viral challenge (12).

Mupapillomavirus HPV1 and HPV63, and Gammapapillomavirus 1 HPV4 and HPV65

The HPV1 E10 protein (formerly named E8) was first noted by Danos and colleagues (13). The existence of this protein in HPV1, HPV63, HPV4 and HPV65 was also noted by Nonnenmacher and colleagues (11), and HPV1 E10 is also described by Garcia-Vallve and colleagues (14).

Gammapapillomavirus species 6

HPV101, 103 and 108 lack a canonical E6 ORF, but potentially encode a highly hydrophobic (E5-like) protein from an overlapping open reading frame, now designated E10 (15).

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  2. Danos O, Engel LW, Chen EY, Yaniv M, Howley PM. 1983. Comparative analysis of the human type 1a and bovine type 1 papillomavirus genomes. JVirol 46:557-566.
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  7. O'Brien V, Campo MS. 1998. BPV-4 E8 transforms NIH3T3 cells, up-regulates cyclin A and cyclin A-associated kinase activity and de-regulates expression of the cdk inhibitor p27Kip1. Oncogene 17:293-301.
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  10. Harry JB, Wettstein FO. 1996. Transforming properties of the cottontail rabbit papillomavirus oncoproteins Le6 and SE6 and of the E8 protein. JVirol 70:3355-3362.
  11. Nonnenmacher M, Salmon J, Jacob Y, Orth G, Breitburd F. 2006. Cottontail rabbit papillomavirus E8 protein is essential for wart formation and provides new insights into viral pathogenesis. JVirol 80:4890-4900.
  12. Hu J, Han R, Cladel NM, Pickel MD, Christensen ND. 2002. Intracutaneous DNA vaccination with the E8 gene of cottontail rabbit papillomavirus induces protective immunity against virus challenge in rabbits. Journal of virology 76:6453-6459.
  13. Danos O, Katinka M, Yaniv M. 1982. Human papillomavirus 1a complete DNA sequence: a novel type of genome organization among papovaviridae. EMBO J 1:231-236.
  14. Garcia-Vallve S, Alonso A, Bravo IG. 2005. Papillomaviruses: different genes have different histories. Trends Microbiol 13:514-521.
  15. Van Doorslaer K, McBride AA. 2016. Molecular archeological evidence in support of the repeated loss of a papillomavirus gene. Sci Rep 6:33028.