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Supplementary Figure 2 from Murine Gammaherpesvirus 68 Infection of IFNγ Unresponsive Mice: A Small Animal Model for Gammaherpesvirus-Associated B-Cell Lymphoproliferative Disease

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posted on 2023-03-30, 18:49 authored by Katherine S. Lee, Steve D. Groshong, Carlyne D. Cool, Bette K. Kleinschmidt-DeMasters, Linda F. van Dyk
Supplementary Figure 2 from Murine Gammaherpesvirus 68 Infection of IFNγ Unresponsive Mice: A Small Animal Model for Gammaherpesvirus-Associated B-Cell Lymphoproliferative Disease

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ARTICLE ABSTRACT

Gammaherpesviruses are tightly controlled by the host immune response, with gammaherpesvirus-associated malignancies prevalent in immune-suppressed individuals. Previously, infection of IFNγ-unresponsive mice with gammaherpesvirus 68 (γHV68) showed that IFNγ controlled chronic infection, limiting chronic diseases including arteritis and pulmonary fibrosis. Here, we show that γHV68-infected IFNγ receptor–deficient (IFNγR−/−) 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 IFNγR−/− mice control chronic γHV68 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 γHV68-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]