Diminished expression of an antiviral ribonuclease in response to pneumovirus infection in vivo.
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.
Moreau
Joanne M
JM
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.
Dyer
Kimberly D
KD
Bonville
Cynthia A
CA
Nitto
Takeaki
T
Vasquez
Nora L
NL
Easton
Andrew J
AJ
Domachowske
Joseph B
JB
Rosenberg
Helene F
HF
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*
D000998:Antiviral Agents; D012333:RNA, Messenger; D012260:Ribonucleases