Murine gammaherpesvirus 68 infection is associated with lymphoproliferative disease and lymphoma in BALB β2 microglobulin-deficient mice

Vera L. Tarakanova, Felipe Suarez, Scott A. Tibbetts, Meagan A. Jacoby, Karen E. Weck, Jay Hess, Samuel H. Speck, Herbert W. Virgin IV

Research output: Contribution to journalArticle

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Abstract

Human gammaherpesvirus infections are associated with development of lymphoproliferative disease. Understanding of the mechanisms of gammaherpesvirus lymphomagenesis during chronic infection in a natural host has been limited by the exquisite species specificity of human gammaherpesviruses and the expense of primates. Murine gammaherpesvirus γHV68 is genetically and biologically related to human gammaherpesviruses and herpesvirus saimiri and has been reported to be associated with lymphoproliferative disease in mice (N. P. Sunil-Chandra, J. Arno, J. Fazakerley, and A. A. Nash, Am. J. Pathol. 145:818-826, 1994). We report the development of an animal model of γHV68 lymphomagenesis in BALB/c β2 microglobulin-deficient mice (BALB β2m-/-). γHV68 infection induced two lymphoproliferative lesions: B-cell lymphoma and atypical lymphoid hyperplasia (ALH). ALH lesion histology resembled lesions of Epstein-Barr virus-associated posttransplant lymphoproliferative disease and was characterized by the abnormal infiltration of the white pulp with cells expressing the plasma cell marker CD138. Lymphomas observed in γHV68-infected animals were B220+/CD3- large-cell lymphomas. γHV68-infected cells were common in ALH lesions as measured by in situ hybridization with a probe specific for viral tRNAs (vtRNAs), but they were scarce in γHV68-infected spleens with normal histology. Unlike ALH lesions, γHV68 vtRNA-positive cells were rare in lymphomas. γHV68 infection of BALB β2m-/- mice results in lymphoproliferation and lymphoma, providing a valuable tool for identifying viral and host genes involved in gammaherpesvirus-associated malignancies. Our findings suggest that γHV68 induces lymphomas via hit-and-run oncogenesis, paracrine effects, or stimulation of chronic inflammation.

Original languageEnglish (US)
Pages (from-to)14668-14679
Number of pages12
JournalJournal of Virology
Volume79
Issue number23
DOIs
StatePublished - Dec 2005
Externally publishedYes

Fingerprint

Murid herpesvirus 4
lymphoma
Lymphoma
lesions (animal)
Hyperplasia
hyperplasia
mice
Infection
infection
Histology
Saimiriine Herpesvirus 2
histology
Saimiriine herpesvirus 2
Species Specificity
cells
Viral Genes
B-Cell Lymphoma
Human herpesvirus 4
Transfer RNA
Plasma Cells

ASJC Scopus subject areas

  • Immunology

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Murine gammaherpesvirus 68 infection is associated with lymphoproliferative disease and lymphoma in BALB β2 microglobulin-deficient mice. / Tarakanova, Vera L.; Suarez, Felipe; Tibbetts, Scott A.; Jacoby, Meagan A.; Weck, Karen E.; Hess, Jay; Speck, Samuel H.; Virgin IV, Herbert W.

In: Journal of Virology, Vol. 79, No. 23, 12.2005, p. 14668-14679.

Research output: Contribution to journalArticle

Tarakanova, Vera L. ; Suarez, Felipe ; Tibbetts, Scott A. ; Jacoby, Meagan A. ; Weck, Karen E. ; Hess, Jay ; Speck, Samuel H. ; Virgin IV, Herbert W. / Murine gammaherpesvirus 68 infection is associated with lymphoproliferative disease and lymphoma in BALB β2 microglobulin-deficient mice. In: Journal of Virology. 2005 ; Vol. 79, No. 23. pp. 14668-14679.
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AU - Hess, Jay

AU - Speck, Samuel H.

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