The pneumonia virus of mice infection model for severe respiratory syncytial virus infection: identifying novel targets for therapeutic intervention

Pneumonia virus of mice (PVM) is the first infection model that replicates features of severe human respiratory syncytial virus (hRSV) disease in the mouse. The PVM model has highlighted the importance of inflammation to the pathogenesis of severe disease, demonstrating that the inflammatory response remains active and acute even when virus replication ceases in response to appropriate antiviral therapy. The fact that the inflammatory response continues and is not completely linked to ongoing virus replication indicates the need for concurrent anti-inflammatory or, ideally, specific immunomodulatory therapy. The chemokine macrophage inflammatory protein-1alpha (MIP-1alpha) and its receptor, CC chemokine receptor I (CCR1), have been identified as crucial to the inflammatory response to PVM and hRSV and thus as elements to exploit for potential immunomodulatory control. Biochemical blockade of MIP-1alpha signaling with the CCR1 antagonist met-RANTES prevents the inflammatory response to PVM and results in reduced morbidity and mortality when administered in conjunction with the antiviral agent ribavirin. Ongoing exploration into the biology of PVM infection will identify other pathways and targets to be exploited for immunomodulatory control of hRSV and related severe respiratory virus infections. (C) 2004 Elsevier Inc. All rights reserved.