Recombinant HPV 16 and 18 Antigens

Structure of HPV

HPV is a relatively small, non-enveloped, epitheliotropic, double-stranded DNA viruses. The genomes of HPV contain three functional parts ORFs.

1. The early (E) region (E1, E2, E3, E4, E5, E6, E7)
2. The late (L) region (L1 and L2)
3. The long control region (LCR)

Fig. 1 HPV structure and genome organization (Modrow, et al. 2010 and Stanley. 2012)

• E1 uses ATP to exert a helicase activity that forces apart the DNA strands, thus preparing the viral genome for replication by cellular DNA replication factors.
• E2 facilitates the binding of E1 to the viral origin of replication. E2 also utilizes a cellular protein known as Bromodomain-4 (Brd4) to tether the viral genome to cellular chromosomes.
• E3 gene exists only in a few papillomavirus types. The gene is not known to be expressed as a protein and does not appear to serve any function.
• E4 protein of many papillomavirus types is thought to facilitate virion release into the environment by disrupting intermediate filaments of the keratinocyte cytoskeleton. E4 also participate in arresting cells in the G2 phase of the cell cycle.
• E5 are hydrophobic proteins that destabilize the function of many membrane proteins in the infected cell. The E5 proteins seem to activate the signal cascade initiated by epidermal growth factor upon ligand binding.
• E6 mediate the degradation of p53, a major tumor suppressor protein, reducing the ability to respond to DNA damage. E6 has also been shown to target other cellular proteins, thereby altering several metabolic pathways.
• E7 protein is to inactivate members of the pRb family of tumor suppressor proteins. Together with E6, E7 serves to prevent apoptosis and promote cell cycle progression, thus priming the cell for replication of the viral DNA.
• L1 spontaneously self-assembles into pentameric capsomers. Purified capsomers can go on to form capsids, which are stabilized by disulfide bonds between neighboring L1 molecules. L1 capsids assembled in vitro are the basis of prophylactic vaccines against several HPV types.
• L2 cooperate with L1 to package the viral DNA into the virion. L2 has been shown to interact with a number of cellular proteins during the infectious entry process.