title: Inflammatory responses to pneumovirus infection in IFN-alpha beta R gene-deleted mice.
abstract: Pneumonia virus of mice (PVM; family Paramyxoviridae) is a natural pathogen of rodents that reproduces important clinical features of severe respiratory syncytial virus infection in humans. As anticipated, PVM infection induces transcription of IFN antiviral response genes preferentially in wild-type over IFN-alphabetaR gene-deleted (IFN-alphabetaR-/-) mice. However, we demonstrate that PVM infection results in enhanced expression of eotaxin-2 (CCL24), thymus and activation-regulated chemokine (CCL17), and the proinflammatory RNase mouse eosinophil-associated RNase (mEar) 11, and decreased expression of monocyte chemotactic protein-5, IFN-gamma-inducible protein-10, and TLR-3 in lung tissue of IFN-alphabetaR-/- mice when compared with wild type. No differential expression of chemokines MIP-1alpha or MIP-2 or Th2 cytokines IL-4 or IL-5 was observed. Differential expression of proinflammatory mediators was associated with distinct patterns of lung pathology. The widespread granulocytic infiltration and intra-alveolar edema observed in PVM-infected, wild-type mice are replaced with patchy, dense inflammatory foci localized to the periphery of the larger blood vessels. Bronchoalveolar lavage fluid from IFN-alphabetaR-/- mice yielded 7- to 8-fold fewer leukocytes overall, with increased percentages of eosinophils, monocytes, and CD4+ T cells, and decreased percentage of CD8+ T cells. Differential pathology is associated with prolonged survival of the IFN-alphabetaR-/- mice (50% survival at 10.8 +/- 0.6 days vs the wild type at 9.0 +/- 0.3 days; p < 0.02) despite increased virus titers. Overall, our findings serve to identify novel transcripts that are differentially expressed in the presence or absence of IFN-alphabetaR-mediated signaling, further elucidating interactions between the IFN and antiviral inflammatory responses in vivo.
authors.affiliation: Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Tara L
authors.initials: TL
authors.lastname: Garvey
authors.forename: Kimberly D
authors.initials: KD
authors.lastname: Dyer
authors.forename: John A
authors.initials: JA
authors.lastname: Ellis
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Bonville
authors.forename: Barbara
authors.initials: B
authors.lastname: Foster
authors.forename: Calman
authors.initials: C
authors.lastname: Prussin
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Easton
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Domachowske
authors.forename: Helene F
authors.initials: HF
authors.lastname: Rosenberg
mesh_terms: D000818:Animals; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D054357:Chemokine CXCL10; D054426:Chemokine CXCL2; D018925:Chemokines / Q000096:biosynthesis; D019743:Chemokines, CXC / Q000096:biosynthesis / Q000235:genetics; D017353:Gene Deletion; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000821:virology; D007370:Interferon Type I / Q000096:biosynthesis / Q000235:genetics; D007962:Leukocytes / Q000473:pathology; D008168:Lung / Q000276:immunology / Q000473:pathology* / Q000821:virology; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018945:Monocyte Chemoattractant Proteins / Q000096:biosynthesis / Q000235:genetics; D018111:Pneumovirus / Q000276:immunology* / Q000502:physiology; D018186:Pneumovirus Infections / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D017471:Receptors, Interferon / Q000172:deficiency* / Q000235:genetics*; D014779:Virus Replication / Q000502:physiology
chemical_list: C491224:Ccl12 protein, mouse; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D054357:Chemokine CXCL10; D054426:Chemokine CXCL2; D018925:Chemokines; D019743:Chemokines, CXC; C404915:Cxcl2 protein, mouse; D007370:Interferon Type I; D019402:Macrophage Inflammatory Proteins; D018945:Monocyte Chemoattractant Proteins; D012333:RNA, Messenger; D017471:Receptors, Interferon