HPV Life Cycle

This web page was produced as an assignment for an undergraduate course at Davidson College.

Human papillomaviruses are divided into three main supergroups: A, B, and E. Supergroup A encompasses all genitally transmitted papillomaviruses, as well as some cutaneous viruses. The genitally transmitted viruses present as mucosal lesions, while the cutaneous variety are the primary cause of skin warts. Viruses in supergroup B also form cutaneous warts similar to those from group A, and they are one cause of non-melanoma skin cancer. Supergroup E is comprised of a third type of virus that causes cutaneous warts.

The HPV genome is a double-stranded DNA that codes for eight proteins. These proteins are named for when they are expressed during the virus’s occupation of its host: early (E) and late (L). E1, 2, 4, and 5 are important to genome replication. E1 also prevents the virus’s genome from integrating into the host’s genome, and initiates gene expression when complexed with E2. E6 and E7 are oncogenes, and, unchecked, can cause tumorous growth of the host cell. E2 and E4 normally inhibit this action. The late proteins, L1 and L2, are capsid proteins and are thus only expressed when the virus copies are repackaged to be released from the host cell (Doorbar 2005; Stanley 2006).

All HPV develop and reproduce solely in keratinocytes, or keratin-producing epithelial cells, the differentiation of which is critical to the papillomavirus’s own development. The virus first infects keratinocyte stem cells, which live in the basal layer of the epithelium, through a breach in the upper layers of the epithelium. Upon infection, the virus takes advantage of the cell’s replication machinery to reproduce its genome several times, so that each infected cell contains a low viral load of about 50 copies. As the cells proliferate, they move towards the outer layers of the epithelium; the viruses proliferate as well, but do not amplify their genome to escape detection by the immune system. When the host keratinocyte reaches S-phase in the differentiation compartment of the epithelium, the papillomavirus replicates its genome to the critical limit of about 1000 copies. In fact, the virus releases growth promoters E6 and E7 at this stage in order to stimulate the host’s movement into this phase. When the keratinocyte reaches the superficial epithelium and dies, the genomes are repackaged into capsids and shed from the cell (Doorbar 2005; Stanley 2006).