Polyomaviruses of Nonhuman Primates: Implications for Research

Polyomaviruses are a family of small nonenveloped DNA viruses that infect birds and mammals. At least 7 nonhuman primate polyomaviruses that occur in macaques, African green monkeys, marmosets baboons, and chimpanzees have been described, as well as 4 polyomaviruses that occur in humans. Simian virus 40 (SV40), which infects macaques, was the first nonhuman primate polyomavirus identified as a contaminant of early polio vaccines. Primate polyomaviruses cause inapparent primary infections but persist in the host and can cause severe disease in situations of immunocompromise. This review describes the primate polyomaviruses, and the diseases associated with the viruses of macaques. In macaques, the greatest current concerns are the potential confounding of study results by polyomavirus infections and the zoonotic potential of SV40.Abbreviations: PML, progressive multifocal leukoencephalopathy; SV40, Simian virus 40Polyomaviruses were previously members of the family Papovaviridae, which included (and derived its name from) rabbit papilloma virus (pa), mouse polyoma virus (po), and simian vacuolating virus (va). Papovaviruses are nonenveloped viruses, with double-stranded circular DNA and an icosahedral capsule. Since the 1980s, studies of Simian virus 40 (SV40) and mouse polyomavirus have demonstrated that these viruses have smaller capsids (45 nm versus 50 nm), smaller genomes (5 kb versus 8 kb), and a different genomic organization than those of papillomaviruses. SV40 and mouse polyomavirus now form an independent family, Polyomaviridae.¹⁸More than 13 members of Polyomaviridae infect mammals and birds. The first polyomavirus was discovered in 1953 in mice²⁸ and was so named because it caused tumors at multiple sites in neonatal mice. Indeed oncogenicity is a common feature of polyomaviruses, particularly tumor production in non-native hosts. Various members of the group transform cell lines and immortalize primary cell cultures as well as induce tumors in susceptible animals. SV40 was identified in 1960 in primary macaque kidney cell cultures, as a contaminant of polio vaccines.⁶⁸ In 1971, the human polyomaviruses BKV²³ and JCV⁵⁴ were identified (both are named after the initials of the patients in which they were first recognized). JCV was discovered in the brain of a patient with progressive multifocal leukoencephalopathy, and BKV was found in the urine of a renal transplant patient. Recently, 2 additional polyomaviruses of the nasopharynx of humans, KIV and WUV, have been identified^2,25 through the use of molecular techniques. KIV was found in nasopharyngeal samples from patients with respiratory disease, and WUV initially was detected in a child with pneumonia. KIV and WUV are closely related genetically and may form a new subfamily of polyomaviruses: their early coding regions (T antigens) are similar to those of other primate polyomaviruses, but their late regions (structural proteins) differ.^7,25 Both KIV and WUV appear to be geographically widespread.The capsids of the polyomaviruses contain 3 structural proteins: VP1, the major capsid protein, and VP2 and VP3, which enclose a single molecule of viral DNA. The viruses also encode regulatory proteins, the T (tumor) antigens. SV40 and other primate polyomaviruses encode 2 T antigens, large T and small t, whereas mouse polyomavirus and some of the other family members have a third, middle T antigen. The T antigens of SV40, BKV, and JCV have about 75% amino-acid homology.⁵⁸ The T antigen of SV40 is essential for initiation of viral DNA replication and promotes transformation and immortalization of host cells, partially through binding to and inhibiting tumor suppressor proteins p53, p107, p130 (pRb2), and pRb (reviewed in reference 10).