β2-microglobulin knockout mice are highly susceptible to polyoma virus tumorigenesis

Donald R. Drake, Aron Lukacher

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Polyoma virus is highly oncogenic when inoculated into immunocompromised adult mice and neonatal mice of specific inbred strains. Although T lymphocytes are known to be essential in controlling polyoma virus tumorigenesis, the importance of class I MHC-restricted CD8+ T cells in mediating tumor resistance remains unclear. Here, we investigated the tumorigenicity of polyoma virus in adult mice rendered CD8+ T cell-deficient by homozygous (-/-) disruption of the β2-microglobulin (β2m) or CD8α (CD8) genes. Nearly all (94%) of the virus-infected adult C57BL/6β2m(-/-) mice developed tumors, and 20% of the virus-inoculated adult C57BL/6CD8(-/-) mice developed hindlimb paralysis, which is indicative of vertebral tumors. Only 2 of 20 virus-inoculated adult normal C57BL/6 mice developed tumors. Despite these different tumor susceptibilities, persistent viral DNA was detected in multiple organs of mice of all three strains. Multifocal lymphoplasmacytic interstitial infiltrates were present in the kidneys and lungs of virus-infected C57BL/6β2m(-/-) and in the lungs of virus- inoculated C57BL/6CD8(-/-) mice. These infiltrates were corn posed primarily of B cells and colocalized with staining for the major vital capsid protein, VP1. No infiltrates or VP1 staining was detected in the kidneys of infected C57BL/6 mice. Using a highly sensitive RT-PCR bioluminescence immunoassay, we investigated and detected persistent polyoma T protein and VP1 messages in both C57BL/6β2m(-/-) and C57BL/6 mice. C57BL/6β2m(-/-) and C57BL/6 mice had equivalent serum virus-neutralizing antibody titers. These results provide in vivo evidence that class I MHC-restricted CD8+ T cells are involved in mediating protection against polyoma virus tumor development.

Original languageEnglish (US)
Pages (from-to)275-284
Number of pages10
JournalVirology
Volume252
Issue number1
DOIs
StatePublished - Dec 5 1998

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Polyomavirus
Inbred C57BL Mouse
Knockout Mice
Carcinogenesis
Viruses
T-Lymphocytes
Neoplasms
Staining and Labeling
Kidney
Oncogenic Viruses
Lung
Inbred Strains Mice
Viral DNA
Capsid Proteins
Hindlimb
Neutralizing Antibodies
Immunoassay
Paralysis
Zea mays
B-Lymphocytes

All Science Journal Classification (ASJC) codes

  • Virology

Cite this

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title = "β2-microglobulin knockout mice are highly susceptible to polyoma virus tumorigenesis",
abstract = "Polyoma virus is highly oncogenic when inoculated into immunocompromised adult mice and neonatal mice of specific inbred strains. Although T lymphocytes are known to be essential in controlling polyoma virus tumorigenesis, the importance of class I MHC-restricted CD8+ T cells in mediating tumor resistance remains unclear. Here, we investigated the tumorigenicity of polyoma virus in adult mice rendered CD8+ T cell-deficient by homozygous (-/-) disruption of the β2-microglobulin (β2m) or CD8α (CD8) genes. Nearly all (94{\%}) of the virus-infected adult C57BL/6β2m(-/-) mice developed tumors, and 20{\%} of the virus-inoculated adult C57BL/6CD8(-/-) mice developed hindlimb paralysis, which is indicative of vertebral tumors. Only 2 of 20 virus-inoculated adult normal C57BL/6 mice developed tumors. Despite these different tumor susceptibilities, persistent viral DNA was detected in multiple organs of mice of all three strains. Multifocal lymphoplasmacytic interstitial infiltrates were present in the kidneys and lungs of virus-infected C57BL/6β2m(-/-) and in the lungs of virus- inoculated C57BL/6CD8(-/-) mice. These infiltrates were corn posed primarily of B cells and colocalized with staining for the major vital capsid protein, VP1. No infiltrates or VP1 staining was detected in the kidneys of infected C57BL/6 mice. Using a highly sensitive RT-PCR bioluminescence immunoassay, we investigated and detected persistent polyoma T protein and VP1 messages in both C57BL/6β2m(-/-) and C57BL/6 mice. C57BL/6β2m(-/-) and C57BL/6 mice had equivalent serum virus-neutralizing antibody titers. These results provide in vivo evidence that class I MHC-restricted CD8+ T cells are involved in mediating protection against polyoma virus tumor development.",
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β2-microglobulin knockout mice are highly susceptible to polyoma virus tumorigenesis. / Drake, Donald R.; Lukacher, Aron.

In: Virology, Vol. 252, No. 1, 05.12.1998, p. 275-284.

Research output: Contribution to journalArticle

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