Polyomavirus tumor induction in mice: effects of polymorphisms of VP1 and large T antigen

Author:

Freund R1,Calderone A1,Dawe C J1,Benjamin T L1

Affiliation:

1. Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115.

Abstract

By testing recombinants between "high tumor" (inducing a high incidence of tumors) and "low tumor" (inducing a low incidence of tumors) strains of polyomavirus, we have previously shown that the key determinant(s) for induction of a high tumor profile resides in coding regions of the high tumor strain (R. Freund, G. Mandel, G. G. Carmichael, J. P. Barncastle, C. J. Dawe, and T. L. Benjamin, J. Virol. 61:2232-2239, 1987). Three single-amino-acid differences between the PTA (high tumor) and RA (low tumor) virus strains have now been identified by DNA sequencing, one each in the large T antigen, in the region common to the middle and small T antigens, and in the major capsid protein VP1. Further tests of appropriate recombinants and oligonucleotide-induced mutants show that VP1 of PTA is the major determinant for induction of a high tumor profile, including all tumors of epithelial origin. The differential effect of the VP1s of PTA and RA on the tumor profile is discussed in terms of a likely contribution of the polymorphic region of VP1 to binding of receptors and infection of different cell types in the animal. The polymorphism in the large T antigen has a more restricted action, which is seen only when tested in virus carrying the VP1 type of PTA; the PTA large T antigen then promotes more rapid growth of tumors of salivary gland and thymus than the RA large T antigen.

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

Reference26 articles.

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3. Multiple binding sites for polyomavirus large T antigen within regulatory sequences of polyomavirus DNA;Cowie A.;J. Virol.,1984

4. Variations in polyoma virus genotype in relation to tumor induction in mice: characterization of wild type strains with widely differing tumor profiles;Dawe C. J.;Am. J. Pathol.,1987

5. Polyomavirus replication in mice: influences of VP1 type and route of inoculation;Dubensky T. W.;J. Virol.,1991

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