Table 2.

Summary of PV proteins

Replication proteins
E1	- Recognition of origin of replication (ori). - binds to E2 protein, resulting in E1-E2 complex. - participates in the recruitment of host cell replication proteins. - exhibits intrinsic ATPase/helicase activity.
E2	- Acts as E6 and E7 transcriptional regulator. - participates in the maintenance of the viral genome in its episomal form by promoting binding between these genomes and mitotic chromosomes during cell division.
E4	- The most expressed protein of PVs and an important hallmark of PVs' pathogenic activity. - occurs abundantly in the cytoplasm of the differentiated keratinocytes of papillomas. - Unlike E1 & E2, E4 is produced later in the differentiation process. HPV16 E4 has also been associated with the collapse of cytokeratin filaments, which thus suggests an auxiliary function in the process of viral exit from cells.
Oncoproteins
E5	- Can induce both in vivo and in vitro transformation.
	- The major BPV oncoprotein. - Disrupt the Golgi complex leading to Inhibiting the expression of MHC-I and cyclooxygenase (COX). (An evolutionary mechanism of immune evasion). - Bind to PDGFR ending with promoting cell cycle deregulation, stimulating angiogenesis. - interferes with normal gap junctions. - disturbs the actin cytoskeleton. - increases the motility of transformed cells. - Disrupting the cell cycle during a productive BPV infection. These mechanisms contribute to viral infection persistence - Most of the tumors of cattle affected by enzootic hematuria express BPV2 E5. - HPV E5 has weak transforming activity, in contrast to its bovine counterpart, BPV1 E5, which shows strong transforming activity.
E6	- A small oncoprotein without enzymatic activity. - Characterized by the presence of a class I PDZ domain, (found in BPV and high-risk HPVs). - BPV and HPV E6 oncoprotein promotes p53 downregulation. - Inducing cell transformation and immortalization due to the up-regulation of telomerases. - BPV E6 protein binds paxillin, which correlates with its transformation function. - prevents apoptosis by degrading p53. - prolongs cell life by telomerase activation. - binds to PDZ domains within several proteins involved in cell polarity, proliferation, and signaling.
E7	- binds to proteins of the retinoblastoma family (RB), - regulate the expression of genes during the S-phase of the cell cycle. - binds and degrades key regulators of cell cycling, including retinoblastoma protein (pRb), p107, and p130.
Capsid proteins
L1	- used in PVs virus classification into different types (able to self-organize in pentameric structures that compose the viral capsid). - Allowing the capsid anchorage to heparin sulfate receptors present in the cell membrane. - L1 immunodetection has been considered the main evidence of productive infection, (the virus assembly). - C-terminal of L1 plays a cardinal part in BPV’s infection and immunogenicity. - produce VLPs that identical to that of intact viral particles. - Strongly immunogenic inducing production of neutralizing antibodies.
L2	Component of the viral capsid.
Virus-like particles (VLPs) can be produced using prokaryotic and eukaryotic systems to express a combination of L1 and L2 or L1 alone
L3	A third structural protein (L3). Present exclusively in BPV-4. However, its function remains unclear.