title: Severe murine lung immunopathology elicited by the pathogenic equine herpesvirus 1 strain RacL11 correlates with early production of macrophage inflammatory proteins 1alpha, 1beta, and 2 and tumor necrosis factor alpha.
abstract: 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 comparison to infection with the attenuated vaccine candidate strain KyA. Intranasal infection with KyA resulted in almost no inflammatory infiltration in the lung. In contrast, infection with the pathogenic RacL11 strain induced a severe alveolar and interstitial inflammation, consisting primarily of lymphocytes, macrophages, and neutrophils. Infection with either EHV-1 strain resulted in the accumulation of similar numbers and ratios of CD4 and CD8 T lymphocytes in the lung and bronchoalveolar lavage (BAL) fluid. Further analysis of these T-cell populations revealed identical EHV-1-specific cytotoxic 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 1alpha (MIP-1alpha), MIP-1beta, and MIP-2 than were observed for KyA-infected mice. Furthermore, significantly higher levels of transcripts specific for tumor necrosis factor alpha were induced on day 3 postinfection with RacL11 compared with KyA. These findings suggest that the early production of proinflammatory beta chemokines plays a major role in the severe, most often lethal, respiratory inflammatory response induced by the pathogenic EHV-1 strain RacL11.
authors.affiliation: Department of Microbiology and Immunology, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130, USA.
authors.forename: P M
authors.initials: PM
authors.lastname: Smith
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.forename: W D
authors.initials: WD
authors.lastname: Grafton
authors.forename: S R
authors.initials: SR
authors.lastname: Jennings
authors.forename: D J
authors.initials: DJ
authors.lastname: O'Callaghan
mesh_terms: D000818:Animals; D003601:Cytotoxicity Tests, Immunologic; D005260:Female; D005434:Flow Cytometry; D006566:Herpesviridae Infections / Q000276:immunology* / Q000473:pathology / Q000821:virology; D004861:Herpesvirus 1, Equid / Q000276:immunology / Q000472:pathogenicity*; D022283:Herpesvirus Vaccines / Q000276:immunology; D007249:Inflammation / Q000503:physiopathology; D008168:Lung / Q000276:immunology* / Q000473:pathology*; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis*; D051379:Mice; D008808:Mice, Inbred CBA; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
chemical_list: D022283:Herpesvirus Vaccines; D019402:Macrophage Inflammatory Proteins; D014409:Tumor Necrosis Factor-alpha