Almost all papillomaviruses express a spliced transcript that encodes an E8^E2 fusion protein. This protein consists of a short peptide from an ORF designated E8 (overlapping the E1 ORF) fused to the C-terminal domain of E2. The resulting proteins function as repressors of viral transcription and replication.
History of E8^E2 Protein Nomenclature
“The analysis of RNA from HPV1, 5, 11, 16, 18, 31 and 33-positive cells and cottontail rabbit PV (CRPV)-induced papillomas indicated that HPV and CRPV express an RNA homologous to the BPV1 E8/E2 mRNA) (1-9). The respective HPV gene products have been labeled E2C, E8^E2C or E8^E2. Experts in the field (A. Abroi, T.H. Haugen, P.M. Howley, A.A. McBride, P.F. Lambert, F. Stubenrauch, Z.M. Zheng) have now agreed on E8^E2 as the official designation. This text is excerpted from reference (10) “Control of viral replication and transcription by the papillomavirus E8^E2 protein” by Dreer et al.
E5-like proteins located in the E6 position of the bovine Xipapillomaviruses were originally designated E8 but have now been renamed E10
Prediction of the E8^E2 splice product
Most papillomaviruses express a spliced transcript that encodes the E8^E2 fusion protein. This protein consists of a short peptide from an ORF designated E8 (overlapping the E1 ORF) fused to the C-terminal domain of E2. The resulting proteins function as repressors of viral transcription and replication.The E8^E2 proteins were initially described in a handful of viruses (8). Based on sequence comparison it is likely that most PVs have the potential to encode the equivalent of an E8^E2 transcript (11, 12).
During the annotation process PaVE uses published evidence (13) as well as splice-site prediction algorithms. Specifically, a combination of the Spliceview (14) and ASSP (15) methods are used. Finally, homology based approaches were used. In August 2016, the algorithm was further refined based on input from Puustusmaa and Abroi (12).
- Doorbar J, Parton A, Hartley K, Banks L, Crook T, Stanley M, Crawford L. 1990. Detection of novel splicing patterns in a HPV16-containing keratinocyte cell line. Virology 178:254-262.
- Isok-Paas H, Mannik A, Ustav E, Ustav M. 2015. The transcription map of HPV11 in U2OS cells adequately reflects the initial and stable replication phases of the viral genome. Virol J 12:59
- Jeckel S, Loetzsch E, Huber E, Stubenrauch F, Iftner T. 2003. Identification of the E9/E2C cDNA and functional characterization of the gene product reveal a new repressor of transcription and replication in cottontail rabbit papillomavirus. JVirol 77:8736-8744.
- Lace MJ, Anson JR, Thomas GS, Turek LP, Haugen TH. 2008. The E8--E2 gene product of human papillomavirus type 16 represses early transcription and replication but is dispensable for viral plasmid persistence in keratinocytes. J Virol 82:10841-10853.
- Stoler MH, Whitbeck A, Wolinsky SM, Broker TR, Chow LT, Howett MK, Kreider JW. 1990. Human papillomavirus type 1 produces redundant as well as polycistronic mRNAs in plantar warts. J Virol 64:3144-3149
- Rotenberg MO, Chow LT, Broker TR. 1989. Characterization of rare human papillomavirus type 11 mRNAs coding for regulatory and structural proteins, using the polymerase chain reaction. Virology 172:489-497.