Limited effects of Muc1 deficiency on mouse adenovirus type 1 respiratory infection

• Published in: Virus research 2011-09, Vol.160 (1-2), p.351-359
• Main Authors: Nguyen, Y, Procario, Megan C., Ashley, Shanna L., O’Neal, Wanda K., Pickles, Raymond J., Weinberg, Jason B.
• Format: Article
• Language: English
• Subjects: Adenoviridae - immunology; Adenoviridae - pathogenicity; Adenoviridae Infections - immunology; Adenoviridae Infections - pathology; Adenoviridae Infections - veterinary; Adenoviridae Infections - virology; Adenovirus; Animals; anti-inflammatory activity; bacterial infections; chemokine CCL2; chemokine CCL5; chemokine CXCL1; Cytokines - secretion; humans; inflammation; Lung - virology; lungs; Mice; Mice, Inbred C57BL; Mice, Knockout; Muc1; Mucin; Mucin-1 - immunology; mucins; mucus; pathogenesis; respiratory tract diseases; Respiratory Tract Infections - immunology; Respiratory Tract Infections - pathology; Respiratory Tract Infections - veterinary; Respiratory Tract Infections - virology; Rodent Diseases - immunology; Rodent Diseases - pathology; Rodent Diseases - virology; tumor necrosis factor-alpha; Viral Load
• ISSN: 0168-1702; 1872-7492
• DOI: 10.1016/j.virusres.2011.07.012

► We used MAV-1 to determine the role of Muc1 in adenovirus pathogenesis. ► MAV-1 did not increase lung Muc1 production. ► MAV-1 viral loads were higher in the lungs of Muc1-deficient mice. ► Muc1 deficiency did not affect MAV-1-induced lung inflammation. ► Muc1 likely contributes to a physical barrier protecting against MAV-1 infection. Muc1 (MUC1 in humans) is a membrane-tethered mucin that exerts anti-inflammatory effects in the lung during bacterial infection. Muc1 and other mucins are also likely to form a protective barrier in the lung. We used mouse adenovirus type 1 (MAV-1, also known as MAdV-1) to determine the role of Muc1 in the pathogenesis of an adenovirus in its natural host. Following intranasal inoculation of wild type mice, we detected increased TNF-α, a cytokine linked to Muc1 production, but no consistent changes in the production of lung Muc1, Muc5ac or overall lung mucus production. Viral loads were modestly higher in the lungs of Muc1−/− mice compared to Muc1+/+ mice at several early time points but decreased to similar levels by 14 days post infection in both groups. However, cellular inflammation and the expression of CXCL1, CCL5, and CCL2 did not significantly differ between Muc1−/− and Muc1+/+ mice. Our data therefore suggest that Muc1 may contribute to a physical barrier that protects against MAV-1 respiratory infection. However, our data do not reveal an anti-inflammatory effect of Muc1 that contributes to MAV-1 pathogenesis.