This Article Full Text Full Text (PDF) Supplementary Data All Versions of this Article: 0008-5472.CAN-09-0291v1 69/13/5481    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Google Scholar Articles by Lee, K. S. Articles by van Dyk, L. F. PubMed PubMed Citation Articles by Lee, K. S. Articles by van Dyk, L. F.

Murine Gammaherpesvirus 68 Infection of IFN Unresponsive Mice: A Small Animal Model for Gammaherpesvirus-Associated B-Cell Lymphoproliferative Disease

Departments of ¹ Microbiology, ² Immunology, and ³ Pathology, University of Colorado Denver School of Medicine, Aurora, Colorado; and ⁴ Department of Medicine, National Jewish Health, Denver, Colorado

Requests for reprints: Linda F. van Dyk, Departments of Microbiology and Immunology, University of Colorado Denver School of Medicine, Mail Stop 8333, 12800 East 19th Avenue, P.O. Box 6511, Aurora, CO 80045. Phone: 303-724-4207; Fax: 303-724-4226; E-mail: linda.vandyk{at}ucdenver.edu.

Gammaherpesviruses are tightly controlled by the host immune response, with gammaherpesvirus-associated malignancies prevalent in immune-suppressed individuals. Previously, infection of IFN-unresponsive mice with gammaherpesvirus 68 (HV68) showed that IFN controlled chronic infection, limiting chronic diseases including arteritis and pulmonary fibrosis. Here, we show that HV68-infected IFN receptor–deficient (IFNR^–/–) mice uniformly develop angiocentric inflammatory lesions in the lung. Prolonged infection revealed a range of outcomes, from spontaneous regression to pulmonary lymphoma. By 12 months of infection, 80% of mice had lymphoid hyperplasia or pulmonary lymphoma; 45% of infected mice developed frank tumors between 5 and 12 months postinfection, with some mice showing systemic involvement. Lymphomas were composed of B lymphocytes and contained latently infected cells. Although IFNR^–/– mice control chronic HV68 infection poorly, both early and late pathologies were indistinguishable between wild-type and reactivation-defective virus infection, indicating that, in contrast with other previously described HV68-associated pathologies, these chronic diseases were not dependent on the reactivation of latent infection. This distinct combination of latent infection and defined host defect led to a specific and consistent lymphoproliferative disease. Significantly, this mouse model of virus-associated pulmonary B-cell lymphoma closely mimics the full spectrum of human lymphomatoid granulomatosis, an EBV-associated malignancy with no effective treatment. [Cancer Res 2009;69(13):5481–9]

This article has been cited by other articles:

				K. S. Lee, C. D. Cool, and L. F. van Dyk Murine Gammaherpesvirus 68 Infection of Gamma Interferon-Deficient Mice on a BALB/c Background Results in Acute Lethal Pneumonia That Is Dependent on Specific Viral Genes J. Virol., November 1, 2009; 83(21): 11397 - 11401. [Abstract] [Full Text] [PDF]