Papovaviruses

Human papillomaviruses (HPV) belong to the papovavirus family have naked icosahedral symmetry and a double stranded small circular DNA genome. HPVs are a family of small DNA viruses with a pronounced tropism for epithelial cells. HPV is transmitted through close direct, often sexual contact and replicates in the epithelium/mucosa. Infection of cells induces cell proliferation and warts. Diagnosis is via papanicolaou (PAP) smears (hybridization with strain specific DNA probes).

Infection with HPV usually causes papillomatous hyperplasia (warts) but lesions cause by a subset of these viruses (e.g., HPV-16, -18, -31, or -33) have a propensity for maligant progression. Warts which are caused by HPV can be surgically removed or spontaneously regress. Laryngeal papillomas require surgery. Currently in Phase II clinical trials are recombinant papillomavirus structural (capsid) protein vaccines which successfully prevent cervical cancer.

During malignant progression, the HPV genome frequently integrates into the host DNA resulting in the expression of only two viral proteins, E6 and E7. The E6 oncoprotein forms a complex with p53 tumor suppressor protein inactivating p53. E7 oncoprotein complex inactivates pRB retinoblastoma tumor suppressor. Strong activation of E6 and E7 oncogenes occurs through disruption of their negative regulator E2 as a result of episomal viral DNA integration into the host DNA.

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