Polyomaviruses

SV40 and polyomavirus shells are constructed from pentamers of the major coat protein with nonequivalent packing but largely equivalent interactions... 

Cidofovir (Fig. 2) has been formally approved for the treatment of CMV retinitis in AIDS patients, where it is administered intravenously at a dose not exceeding 5 mg/kg once weekly during the first two weeks (and every other week thereafter). Cidofovir is also used off label for the treatment of human papilloma virus (HPV) infections (i.e., cutaneous warts, anogenital warts, laryngeal and pharyngeal papilloma), polyomavirus [i.e., progressive (i.e., multifocal leukoencephalopathy (PML)], adenovirus, herpesvirus, and poxvirus (i.e., molluscum contagiosum) infections, where it can be administered intravenously (at a dose of < 5 mg/kg once weekly or every other week) or topically as a 1% gel or cream (De Clercq and Holy 2005). Especially in immunosuppressed patients (i.e., transplant recipients), local treatment of HPV-associated lesions has often yielded spectacular results (Bonatti etal.2007). 

Cidofovir (Vistide) is an acyclic phosphonate cytosine analogue with activity against herpesviruses including CMV, HSV-1, HSV-2, EBV, and VZV. It also inhibits adenoviruses, papillomaviruses, polyomaviruses, and poxviruses. Activation of cidofovir requires metabolism to a diphosphate by host cellular enzymes. Because this activation does not depend upon viral enzymes, similar levels of cidofovir diphosphate are seen in infected and uninfected cells. Cidofovir diphosphate competes with deoxycytidine triphosphate (dCTP) for access to viral... 

Cidofovir is approved for the treatment and prophylaxis of CMV retinitis in AIDS patients. It has also been used in the treatment of acyclovir-resistant (viral thymidine kinase-dehcient) HSV infections, polyomavirus-associated progressive multifocal leukoencephalopathy, condylomata acuminata (anogenital warts), and mollus-cum contagiosum. 

DNA viruses that can trigger tumors are found in the classes of the polyomaviruses, the adenoviruses and the papUloma viruses. The polyoma viruses with the SV40 virus as a well studied representative, adenoma virus and human papUloma virus (HPV) are associated with formation of tumors in humans and have genes coding for proteins with the properties of oncoproteins. The oncoproteins of aU three viruses interfere with the pRb function by Ufting its inhibition of transcription factor E2F. It is assumed that the tumor-promoting activity of the proteins is due, in particular, to this property. 

Larger icosahedral viruses that have been structurally well characterized do not obey the simple quasi-equivalence rule. For example, adenovirus capsids, for which T = 25, are built of 240 hexons (six-coordinated units) that are trimers of the major structural protein, and the 12 pentons consist of a different protein (Burnett 1984). Polyomavirus capsids, for which T = 7, are built of a single major structural protein,... 

Cidofovir is a cytosine nucleotide analog with in vitro activity against CMV, HSV-1, HSV-2, VZV, EBV, HHV-6, HHV-8, adenovirus, poxviruses, polyomaviruses, and human papillomavirus. In contrast to ganciclovir, phosphorylation of cidofovir to the active diphosphate is independent of viral enzymes. After phosphorylation, cidofovir acts both as a potent inhibitor of and as an alternative substrate for viral DNA polymerase, competitively inhibiting DNA synthesis and becoming incorporated into the viral DNA chain. Isolates with resistance to cidofovir have been selected in vitro these isolates tend to be cross-resistant with ganciclovir but retain susceptibility to foscamet. Clinically significant resistance to cidofovir has not been reported to date. 

Other potential uses of cidofovir that are currently under investigation include treatment of the polyomavirus-associated progressive multifocal leukoencephalopathy syndrome in patients with AIDS, postexposure prophylaxis against smallpox, and topical treatment of molluscum contagiosum. Topical cidofovir is not currently available in a standardized preparation. 

Viruses can induce apoptosis of human keratinocytes. These apoptotic cells can express viral antigens and autoantigens, which are coclustered in specific subsets within surface blebs and then cause challenge to self-tolerance if not cleared and processed properly (R15). Andreassen et al. showed that T cell lines specific for polyomavirus T antigen recognize T antigen complexed with nucleosomes and trigger B cells to produce anti-DNA antibodies (A20). 

Elphick GF, Querbes W, Jordan JA, et al. The human polyomavirus JCV, uses serotonin receptors to infect cells. Science 2004 306 1380-1383. 

Muller WJ, Mueller CR, Mes AM, Hassell JA (1983), Polyomavirus origin for DNA replication comprises multiple genetic elements, J. Virol. 47 586-599. 

Zhu ZY, Veldman GM, Cowie A, Carr A, Schaffhausen B, Kamen R (1984), Construction and functional characterization of polyomavirus genomes that separately encode the three early proteins, J. Virol. 51 170-180. 

Montross L, Watkins S, Moreland RB, Mamon H, Caspar DL, Garcea RL (1991), Nuclear assembly of polyomavirus capsids in insect cells expressing the major capsid protein VP1,J. Virol. 65 4991-4998. 

Polyoma- and papillomaviruses share a common capsid structure that is assembled from 72 pentameric capsomeres arranged on a T = 7 icosahedral lattice. Assembly studies of polyomaviruses were first initiated by expression of the major capsid protein of mouse polyomavirus, VPl, in... 

---