| First Author | Lee KS | Year | 2009 |
| Journal | Cancer Res | Volume | 69 |
| Issue | 13 | Pages | 5481-9 |
| PubMed ID | 19531651 | Mgi Jnum | J:150350 |
| Mgi Id | MGI:3850574 | Doi | 10.1158/0008-5472.CAN-09-0291 |
| Citation | Lee KS, et al. (2009) Murine gammaherpesvirus 68 infection of IFNgamma unresponsive mice: a small animal model for gammaherpesvirus-associated B-cell lymphoproliferative disease. Cancer Res 69(13):5481-9 |
| abstractText | Gammaherpesviruses are tightly controlled by the host immune response, with gammaherpesvirus-associated malignancies prevalent in immune-suppressed individuals. Previously, infection of IFNgamma-unresponsive mice with gammaherpesvirus 68 (gammaHV68) showed that IFNgamma controlled chronic infection, limiting chronic diseases including arteritis and pulmonary fibrosis. Here, we show that gammaHV68-infected IFNgamma receptor-deficient (IFNgammaR(-/-)) 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 IFNgammaR(-/-) mice control chronic gammaHV68 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 gammaHV68-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. |
