Perspectives in HPV Secondary Screening and Personalized Therapy Basing on Our Understanding of HPV-Related Carcinogenesis Pathways
Table 3
HPV proteins and their role in viral life cycle.
Protein
Function
E1
Regulator of viral DNA replication. Only protein with enzymatic function. Downregulates host immune response genes.
E2
Initiates viral DNA transcription and partitioning of viral genome. Shifts host immune response.
E3
Ubiquitin ligase activity. Specific function uncertain.
E4
Expressed in middle and upper layers of the epithelium. Disruption of cell cycle and keratin organisation. Arrests cell growth allowing for viral amplification.
E5
Transmembrane protein with a transforming activity. HPV 16-derived E5 targets EGF receptor.
E6
Major oncoprotein. Binds to p53 and allows for its proteolysis.
E7
Major oncoprotein. Binds to RB allowing for E2F to promote cell cycle entry undisturbed.
E8
As E8^E2C limits viral transcription and DNA replication. Plays an important role in keeping a low copy number in undifferentiated squamous epithelium cells. At the same time is up- and downregulated by viral proteins.
L1
Forms the icosahedral capsid—main capsid protein. Has an ability to self-assemble spontaneously and form VLPs.
L2
Minor capsid protein. Plays a role in virus assembly, encapsidation of viral DNA and transport of the virus into the nuclei of infected cells.