The E5 proteins are short, hydrophobic, transmembrane proteins. They are only encoded by a subset of papillomaviruses and are not found in the Beta-, Gamma-, Kappa-, Lambda- or Mu- PVs. Most E5 genes are expressed from the ELR (early to late region) between the E2 and L2 ORFS. Sometimes more than one hydrophobic E5-like protein can be encoded by this region and the proteins are then named E5A and E5B. The PaVE database uses the nomenclature describe by Bravo and Alonso (2004). Unusually, the E5 gene of the Xipapillomaviruses is found in the E6 position. Other than hydrophobicity, there is low sequence similarity among different E5 proteins and they can be further divided into different classes based on phylogeny and hydrophobic profiles.

The best studied E5 proteins are those of BPV1 (delta), BPV4 (xi) and HPV16 (alpha). BPV1 E5 is a dimeric protein that spans the cellular membrane and transforms fibroblasts by binding and activating the platelet derived £]-type growth factor receptor. BPV4 E5 transforms embryonic bovine cells in concert with E7 and HPV16 E5 stimulates proliferation of keratinocytes by activation of the EGF receptor. The E5 proteins interfere with golgi acidification resulting in altered recycling of receptors and MHC Class I molecules to the cell surface and disrupt gap junction-mediated intercellular communication.

Schematic of BPV1E5 membrane protein

BPV1E5 in membrane.

Adapted from figure in Talbert-Slagle and Dimaio, 2009

Nomenclature of E5 proteins used in PaVE

  • E5 proteins derived from Alphapapillomaviruses were named according to the naming scheme suggested Bravo and Alonso (2004) with some modifications. In addition to E5-alpha, E5-beta, E5-gamma and E5-delta we introduce E5-epsilon and E5-zeta.
  • E5-like proteins located in the E6 position of the bovine Xipapillomaviruses were originally designated E8 but have now been renamed E5. Within PaVE these E5 proteins are identified as E5 (E8).
  • Finally, viruses belonging to the Deltapapillomavirus genus encode a protein designated as E5.