Polyoma, virus

The capsids of polyoma virus and the related SV40 have icosahedral symmetry, with 72 pentameric assemblies of the major capsid protein. The pentamers are linked to their neighbors by flexible arms, with a p strand that augments a p sheet in the invaded pentamer. These flexible arms allow the pentamers to be linked together with both fivefold and sixfold symmetry. 

Rayment, I., et al. Polyoma virus capsid structure at 22.5 A resolution. Nature 29S 110-115, 1982. 

Yaffe, D. and Gershon, D. (1967) Multinucleated muscle fibers induction of DNA synthesis and mitosis by polyoma virus infection. Nature 215, 421—424. 

Protein phosphorylation is one of the most important mechanisms in the regulation of cellular function. Proteins can be phosphorylated on serine, threonine or tyrosine residues. Most phosphorylation occurs on serine and threonine, with less than 1% on tyrosine (see Ch. 23). This perhaps accounts for the late discovery of tyrosine phosphorylation, which was found first on polyoma virus middle T antigen in 1979 by Hunter and colleagues [1,2]. 

Albumin, tetanus toxin, autocrine motility factor, interleukin-2, alkaline phosphatase, glycosyl-phosphatidylinositol (GPI)-GFP, polyoma virus, and echo virus 1 (26). 

Idoxuridine (Herplex) is a water-soluble iodinated derivative of deoxyuridine that inhibits several DNA viruses including HSV, VZV, vaccinia, and polyoma virus. The triphosphorylated metabolite of idoxuridine inhibits both viral and cellular DNA synthesis and is also incorporated into DNA. Such modified DNA is susceptible to strand breakage and causes aberrant viral protein synthesis. Because of its significant host cytotoxicity, idoxuridine cannot be used to treat systemic viral infections The development of resistance to this drug is common. 

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. 

Rassoulzadegan, M., Naghashfar, Z., Cowie, a., Carr, A., Grisoni, M., Kamen, R., and CUZIN, F. (1983). Expression of the large T protein of polyoma virus promotes establishment in culture of normal rodent fibroblast cell lines, Proc. NatL Acad. Sci. 80, 4354. 

A surprising finding is that the polyoma virus coat, which was expected to contain 420 (7 x 60) subunits, apparently contains only 360. The result is that the hexavalent morphological unit is a pentamer and that quasi-eqivalence appears... 

Another lead as to how a DNA virus transforms cells is to look at the cellular proteins they influence. There is a striking parallel here between the functions of adenovirus E1B and SV40 big T in this regard. These two genes are required for immortalization or transformation, and they both form a tight association with the cellular protein p53, which is considered to be a good candidate for a protooncogene-related protein. Finally, the polyoma middle-T protein, which is required for transformation by polyoma virus,... 

Dulbecco R, Freeman G (1959), Plaque production by the polyoma virus, Virology 8 396-397. 

Fig. 2.1. Untransformed (1) and Polyoma virus transformed (2) BHK cells show quite different morphology. This is also clear in the appearance of the colonies shown at low power (3) where the transformed colony is compact whereas untransformed cells tend to spread out over the culture surface in parallel arrays. (Reproduced from MacPherson and Stoker, 1962, with permission.)...

This is the situation with BHK 21 hamster fibroblasts (Macpher-son and Stoker, 1962 Stoker and Macpherson, 1964) which still have the correct diploid chromosome number but which are believed to have the incorrect chromosome complement. These cells do, however, exhibit a certain amount of contact inhibition of movement ( 2.4.2) and may be further transformed by treatment with polyoma virus (e.g. to form Py Y cells Fig. 2.1) or SV40 (to form SV28 cells). 

In 1967 Hirt developed a method of selectively extracting the small DNA of SV40 and polyoma viruses while sedimenting the larger cellular DNA. 

The following characteristics have been noted in cells transformed by SV40 or polyoma virus (Tooze, 1973). 

Macpherson (1961) exposed confluent monolayers or cell suspension to virus and then plated the cells at low density. They then picked out transformed colonies by appearance in the absence of any selective pressure (see Fig. 2.1). The number of transformed colonies is directly related to virus dose. When primary hamster kidney cells were exposed to polyoma virus at 96 p.f.u./cell between 1 in 100 and 1 in 5000 cells was transformed. 

Burger and Goldberg30 first reported that, of the sugars found in glycoproteins, only 2-acetamido-2-deoxy-D-glucose andN,]V -diacetyl-chitobiose inhibited the agglutination of polyoma virus-transformed BHK cells and chemically-induced L1210 leukemia cells (compare Refs. 501-504). 

Chapman and Liljas, Fig. 14. The structure of polyoma virus VPl (Stehle and Harrison, 1996). The coloring scheme of strands B through I of the jelly roll is the same as in Fig. 1. The C-terminal arm of a neighboring subunit (purple) is inserted in an extension of the BIDG sheet of the viral jelly-roll domain. 

Treatment with flndarabine resnlts in prolonged immunosuppression lasting over 6 months (15). Patients who are immunocompromised are at risk of infection with chemotherapy. Infection with JC vrrns, a hnman polyoma virus, occurred in two patients after flndarabine treatment of a low-grade lymphoma, which led to a progressive multifocal leukoencephalopathy (16). In one series of 27 patients who received flndarabine, serions infections developed in 24 (17). 

Tor ado GJ, Habel K and Green H (1965) Antigenic and cultural properties of cells doubly transformed by polyoma virus and SV40. Virology 27 179-185. 

Lactate dehydrogenase virus Minute virus of mice Mouse adenovirus Mouse cytomegalovirus Thielers virus Mouse hepatitis virus Mouse rotavirus Pneumonia virus of mice Polyoma virus Retroviruses Thymic virus... 

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