RIG-I overexpression decreases mortality of cigarette smoke exposed mice during influenza A virus infection.

Abstract

BACKGROUND:

Retinoic acid-inducible gene I (RIG-I) is an important regulator of virus-induced antiviral interferons (IFNs) and proinflammatory cytokines which participate in clearing viral infections. Cigarette smoke (CS) exposure increases the frequency and severity of respiratory tract infections.

METHODS:

We generated a RIG-I transgenic (TG) mouse strain that expresses the RIG-I gene product under the control of the human lung specific surfactant protein C promoter. We compared the mortality and host immune responses of RIG-I TG mice and their litter-matched wild type (WT) mice following challenge with influenza A virus (IAV).

RESULTS:

RIG-I overexpression increased survival of IAV-infected mice. CS exposure increased mortality in WT mice infected with IAV. Remarkably, the effect of RIG-I overexpression on survival during IAV infection was enhanced in CS-exposed animals. CS-exposed IAV-infected WT mice had a suppressed innate response profile in the lung compared to sham-exposed IAV-infected WT mice in terms of the protein concentration, total cell count and inflammatory cell composition in the bronchoalveolar lavage fluid. RIG-I overexpression restored the innate immune response in CS-exposed mice to that seen in sham-exposed WT mice during IAV infection, and is likely responsible for enhanced survival in RIG-I TG mice as restoration preceded death of the animals.

CONCLUSIONS:

Our results demonstrate that RIG-I overexpression in mice is protective for CS enhanced susceptibility of smokers to influenza infection, and that CS mediated RIG-I suppression may be partially responsible for the increased morbidity and mortality of the mice exposed to IAV. Thus, optimizing the RIG-I response may be an important treatment strategy for CS-enhanced lung infections, particularly those due to IAV.

• Authors: Xiaoqiu Wang, Wenxin Wu, Wei Zhang, J Leland Booth, Elizabeth S Duggan, Lili Tian, Sunil More, Yan D Zhao, Ravindranauth N Sawh, Lin Liu, Ming-Hui Zou, Jordan P Metcalf
• Journal: Respiratory research (Respir Res) Vol. 18 Issue 1 Pg. 166 (09 02 2017) ISSN: 1465-993X [Electronic] England
• PMID: 28865477 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Tobacco Smoke Pollution
• Ddx58 protein, mouse
• DEAD Box Protein 58

Topics

• Animals
• DEAD Box Protein 58 (biosynthesis, genetics)
• Dogs
• Gene Expression
• Humans
• Influenza A Virus, H1N1 Subtype
• Inhalation Exposure (adverse effects)
• Madin Darby Canine Kidney Cells
• Mice
• Mice, Transgenic
• Mortality (trends)
• Orthomyxoviridae Infections (metabolism, mortality)
• Smoking (adverse effects, metabolism, mortality)
• Tobacco Smoke Pollution (adverse effects)