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Polyomaviruses exhibit asymptomatic persistent infections in humans. They induce tumors in laboratory rodents. The JC type of polyomavirus causes progressive multifocal leukoencephalopathy in humans.
Polyomaviruses are icosahedral, 45-nm diameter particles, with three capsid proteins and no envelope. They contain a 5-kbp circular, double-stranded DNA genome. The genome structure is similar for all members of the polyomavirus group and consists of two or three replicative genes (tumor antigens) encoded on one strand and three structural genes (capsid antigens) encoded on the other strand.
Classification is based on the structure of the viral particle. Human and animal polyomaviruses are antigenically distinct; only one serotype is known for each virus. The prototype is simian virus 40 (SV40) from monkeys.
Viral DNA uncoats in the nuclei of infected cells. Early viral genes are expressed and host cells are stimulated to enter the S phase, providing cellular enzymes that are utilized for viral DNA synthesis. Late viral genes are expressed, and progeny virions are assembled in nuclei. Cell lysis occurs later. Viral particles usually stay associated with cell debris. The papovaviruses have oncogenic potential (the papillomaviruses in their natural hosts and the polyomaviruses under experimental conditions).
Human polyomaviruses establish persistent infections in the kidneys; these infections may reactivate in immunosuppressed hosts and during some normal pregnancies. Progressive multifocal leukoencephalopathy is a rare demyelinating disease of the central nervous system of some immunosuppressed patients. It is caused by replication of JC virus in oligodendrocytes. Although oncogenic in rodents, polyomaviruses are not believed to be important factors in human cancers.
Infections are persistent and induce production of humoral antibodies and cytotoxic T cells. Viral reactivation occurs in immunosuppressed persons. Impaired cell-mediated immunity is the background for the development of progressive multifocal leukoencephalopathy. Interferon is weakly induced by papovaviruses, which vary in their sensitivity to the antiviral action of interferon. Transformation by polyomaviruses can be inhibited by interferon.
BK and JC types of polyomavirus are widespread. Infections occur during childhood, and 70 to 80 percent of adults have antibodies. The route of transmission is unknown, but may be respiratory. Human viruses have no animal reservoirs. A small percentage of humans also possess antibodies to SV40, a simian virus. The mechanism of exposure to SV40 is unknown.
Clinical presentation and the presence of antibodies are the best means of diagnosis.
There are no known control measures.
Clinical manifestations include benign papillomatous lesions of skin and mucous membranes (common warts, plantar warts, flat warts, anogenital warts, epidermodysplasia verruciformis, and laryngeal papillomas). Cervical intraepithelial neoplasia and cervical cancer are associated with human papillomavirus infection.
Papillomaviruses are similar to polyomaviruses, except that the particles are 55 nm in diameter, the DNA is 8 kbp in size, and the genome structure is more complex. All viral genes are encoded on one strand of DNA.
Classification is based on the structure of the viral particle. Reagents are not available for serotyping; human papillomavirus types are distinguished by DNA hybridization assays or DNA sequence analysis. There are more than 70 human types.
Replication is dependent on the differentiated state of epithelial cells. Viral DNA remains latent (not integrated) in basal cells of benign lesions. Replication occurs in differentiating cells. Capsid proteins and viral particles are found only in terminally differentiated epidermal cells. Viral DNA is integrated in cancer cells, which contain no replicating virus.
Different human papillomavirus types cause specific lesions. The pathogenic mechanisms are not well understood. A few specific types, notably human papillomavirus types 16 and 18, are associated with the development of premalignant and malignant genital lesions. Cofactors are required for cancer development.
The roles of humoral and cell-mediated immune responses in disease pathogenesis or prevention are not known. Warts tend to regress spontaneously.
Papillomaviruses are widely distributed. Transmission occurs by contact. Genital warts are sexually transmitted. Laryngeal papillomas may be due to human papillomavirus acquired during birth from a mother with genital warts. Prevalence data are incomplete, and there are no serologic assays to distinguish the different types.
Clinically, nucleic acid hybridization may be used to detect viral DNA in tissue samples. Serologic methods need to be developed to identify specific human papillomavirus types.
Instruments should be sterilized after examination of patients with human papillomavirus infections. The public should be educated about this disease to prevent sexual transmission. Most warts regress spontaneously. Available treatments include local destructive methods and application of caustic agents. Interferons are effective against laryngeal papillomas, common warts, and anogenital warts.
