title: Diminished expression of an antiviral ribonuclease in response to pneumovirus infection in vivo.
abstract: The mouse eosinophil-associated ribonucleases (mEars) are species specific, divergent orthologs of the human antiviral RNase A ribonucleases, eosinophil-derived neurotoxin (RNase 2) and eosinophil cationic protein (RNase 3). We show here that mEar 2 is also an antiviral ribonuclease, as micromolar concentrations promote a approximately sixfold reduction in the infectivity of pneumonia virus of mice (PVM) for target respiratory epithelial cells in vitro. Although initially identified as a component of eosinophilic leukocytes, mEar 2 mRNA and protein were also detected in lung tissue accompanied by enzymatically active mEar 2 in bronchoalveolar lavage fluid (BALF). At t=3 days post-inoculation with PVM (strain J3666), we observed the characteristic inflammatory response accompanied by diminished expression of total mEar mRNA and protein in lung tissue and a corresponding fivefold drop in ribonuclease activity in BALF. No change in mEar expression was observed in response to infection with PVM strain 15, a replication-competent strain of PVM that does not elicit a cellular inflammatory response. However, mEar expression is not directly dependent on inflammation per se, as diminished expression of mEar mRNA and BAL ribonuclease activity were also observed in PVM-infected, inflammation-deficient, MIP-1alpha -/- mice. We propose that this mechanism may represent a novel virus-mediated evasion strategy, with a mechanism that is linked in some fashion to virus-specific pathogenicity.
authors.affiliation: Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 10, Room 11N104, 9000 Rockville Pike, Bethesda, MD 20892, USA.
authors.forename: Joanne M
authors.initials: JM
authors.lastname: Moreau
authors.forename: Kimberly D
authors.initials: KD
authors.lastname: Dyer
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Bonville
authors.forename: Takeaki
authors.initials: T
authors.lastname: Nitto
authors.forename: Nora L
authors.initials: NL
authors.lastname: Vasquez
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; D000998:Antiviral Agents / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D004804:Eosinophils / Q000201:enzymology* / Q000276:immunology; D007249:Inflammation / Q000276:immunology; D008168:Lung / Q000201:enzymology / Q000276:immunology; D051379:Mice; D029122:Murine pneumonia virus / Q000472:pathogenicity*; D018186:Pneumovirus Infections / Q000503:physiopathology* / Q000821:virology; D012333:RNA, Messenger / Q000378:metabolism; D012260:Ribonucleases / Q000235:genetics / Q000378:metabolism*
chemical_list: D000998:Antiviral Agents; D012333:RNA, Messenger; D012260:Ribonucleases