Papillomaviruses and Polyomaviruses Overview

Study Notes

Papillomaviruses were identified as the cause of warts in animals as early as the 9th century.
The viral etiology of papillomas was recognized in 1907.
It was not until 1978 that bovine and other animal papillomas were discovered to be caused by several different viruses.
Bovine papillomatosis, canine oral papillomatosis, and equine sarcoid can present major clinical problems.
Papillomaviruses cannot be grown in cell culture, but their DNA has been sequenced.
Papillomaviruses were discovered to cause cervical, anogenital, and laryngeal carcinomas in humans in the 1980s.
The discovery of papillomaviruses causing cancer in humans stimulated research on the mechanism of papillomavirus oncogenesis.

Polyomaviruses are highly species specific.
Polyomaviruses are generally harmless, except for rare neurologic and urologic diseases in immunocompromised humans and a disease in budgerigars.

The Papovaviridae family consists of two genera: Papillomavirus and Polyomavirus.
The name Papovaviridae refers to the two genera and "vacuolating agent," an old name for the prototype polyomavirus, simian virus 40 (SV40).
Papillomaviruses are distinguished by host range and DNA sequence.
Papillomavirus types are numbered in order of identification.
A new virus type must have less than 50% DNA sequence homology with other viruses from the same species.
Greater than 50% but less than 100% homology defines new subtypes, designated by serial letters.
More than 77 types of human papillomaviruses have been identified.
Papillomaviruses have also been found in chimpanzees, colobus and rhesus monkeys, deer, dogs, elephant, elk, opossum, mice, turtles, chaffinches, and parrots.
There is little sequence homology between DNAs of papillomaviruses from different species.

Bovine papillomaviruses have been classified into two groups:
- Group 1: Bovine papillomaviruses 1, 2, and 5.
- Group 2: Bovine papillomaviruses 3, 4, and 6.
The two groups are only distantly related.
Papillomaviruses can be categorized according to their tissue tropism and the histologic character of the lesions they cause:
- Group I: Cutaneous neoplasia.
- Group II: Hyperplasia of nonstratified squamous epithelium.
- Group III: Subcutaneous fibromas and cutaneous papillomas.
- Group IV: Primarily fibromas with minimal cutaneous hyperplasia.

Papovavirus virions are nonenveloped, spherical, with icosahedral symmetry.
Virions are 55 nm (genus Papillomavirus) or 45 nm (genus Polyomavirus) in diameter.
Virions are constructed from 72 hexavalent capsomers arranged in pentameric arrays.
Both “empty” and “full” virus particles are visible by electron microscopy.
The genome consists of a single molecule of circular double-stranded DNA, 8 kbp (genus Papillomavirus) or 5 kbp (genus Polyomavirus) in size.
The DNA is covalently closed, supercoiled, and infectious.
Six polypeptides have been identified, two forming the capsid.
The viruses are resistant to various environmental insults: infectivity survives lipid solvents, detergents, low pH, and high temperatures.

Papillomavirus replication is tightly linked to the growth and differentiation of cells in stratified squamous and mucosal epithelium.
The replication cycle starts in basal layers and ends with shedding at the epidermal surface.
Papillomaviruses persist in a nonproductive, episomal form, integrating into the host cell genome only upon malignant transformation