Severe murine lung immunopathology elicited by the pathogenic equine herpesvirus 1 strain RacL11 correlates with early production of macrophage inflammatory proteins 1 alpha, 1 beta, and 2 and tumor necrosis factor alpha

The CBA mouse model was used to investigate the immunopathology induced in the lung by the pathogenic equine herpesvirus 1 (EHV-1) strain RacL11 in co mparison to infection with the attenuated vaccine candidate strain KJ A. In tranasal infection with KyA resulted in almost no inflammatory infiltration in the lung. In contrast, infection with the pathogenic RacL11 strain indu ced a severe alveolar and interstitial inflammation, consisting primarily o f lymphocytes, macrophages, and neutrophils. Infection with either EHV-1 st rain resulted in the accumulation of similar numbers and ratios of CD4 and CD8 T lymphocytes in the lung and bronchoalveolar lavage (BAL) fluid. Furth er analysis of these T-cell populations revealed identical EHV-1-specific c ytotoxic T-lymphocyte responses. RNase protection analysis of RNA isolated from the BAL fluid of RacL11-infected mice on day 3 postinfection revealed much higher levels of RNA specific for macrophage inflammatory protein 1 al pha (MIP-1 alpha), MIP-1 beta, and MIP-2 than were observed for KyA-infecte d mice. Furthermore, significantly higher levels of transcripts specific fo r tumor necrosis factor alpha were induced on day 3 postinfection with RacL 11 compared with KyA, These findings suggest that the early production of p roinflammatory beta chemokines plays a major role in the severe, most often lethal, respiratory inflammatory response induced by the pathogenic EHV-1 strain RacL11.