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: Joanne M Moreau, Kimberly D Dyer, Cynthia A Bonville, Takeaki Nitto, Nora L Vasquez, Andrew J Easton, Joseph B Domachowske, Helene F Rosenberg
• Journal: Antiviral research (Antiviral Res) Vol. 59 Issue 3 Pg. 181-91 (Aug 2003) ISSN: 0166-3542 [Print] Netherlands
• PMID: 12927308 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antiviral Agents
• RNA, Messenger
• Ribonucleases

Topics

• Animals
• Antiviral Agents (metabolism)
• Bronchoalveolar Lavage Fluid (immunology)
• Eosinophils (enzymology, immunology)
• Inflammation (immunology)
• Lung (enzymology, immunology)
• Mice
• Murine pneumonia virus (pathogenicity)
• Pneumovirus Infections (physiopathology, virology)
• RNA, Messenger (metabolism)
• Ribonucleases (genetics, metabolism)