Murine CMV Pneumonitis in Allogeneic BMT

University Of Kentucky, Lexington KY

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Abstract

DESCRIPTION (provided by applicant): Despite the practice of antimicrobial prophylaxis, Cytomegalovirus (CMV) infection in immunocompromised patients causes potentially life-threatening disease, especially in recipients of bone marrow transplantation (BMT). CMV-associated pneumonitis is frequently a fatal complication of human CMV (hCMV) disease in BMT recipients. We will study an allogeneic murine BMT model in which BALB/c mice previously infected with murine CMV (MCMV) receive bone marrow from B10.D2 donors. Previous studies have demonstrated that animals previously infected with MCMV exhibit a more severe disease progression following transplantation. To test our hypothesis: The mechanism by which reactivation of latent MCMV infection exacerbates pneumonitis after minor antigen mismatched bone marrow transplantation is through augmentation of T cell infiltration and cytokine production we have developed three specific aims. The specific aims to be addressed are 1) To determine the role of viral replication on the development of IP after allo BMT, 2) To define the role of continued infiltration of T cells into the lungs of previously infected mice in the absence of replicating virus and 3) To determine the role of adhesion molecules in the development of viral interstitial pneumonitis following allo BMT. Using this model we will investigate the role viral replication following reactivation on disease progression. We will examine the specificity of lymphocytes in the lungs using MCMV specific MHC II tetramers and V|33. Also we will investigate the role of viral or host up-regulation of adhesion molecules in recruiting lymphocytes to the lungs. These experiments will provide insights into the interaction of host responses to CMV following BMT and may serve as a basis for developing new strategies to protect and treat BMT patients susceptible to chronic CMV infections. This research will also provide the opportunity for students to participate actively in the solution to an important clinical problem.