Influenza infection results in upregulation of inflammatory and atrophy genes in murine skeletal muscle (VIR5P.1146)

Abstract

Abstract Though influenza is a respiratory infection, myalgia is a common symptom and associations with acute myositis and rhabdomyolysis have been noted. It is currently unclear if these symptoms are secondary due to the systemic response or if muscle may contribute to inflammation. Further, the effect of influenza on muscle damage and potential repair is not well established. We aimed to determine the expression level of select myokines, atrophy, and myogenic markers in skeletal muscle during influenza infection. Young C57BL/6 mice were inoculated with Pr8 influenza virus (IN, 500 EID50) and sacrificed 7 or 15 days post infection (DPI) or were uninfected (n=4/group). Gastrocnemius gene expression was analyzed via RT-qPCR. Myostatin, IL4, IL6, IL6 receptor alpha, Ubiquitin B, Ubiquitin C, Foxo1, Atrogin-1, and MuRF-1 gene expression was upregulated 7 DPI indicating increased inflammation, protein degradation, and atrophy. Expression of positive regulators of muscle growth and maintenance (Igf-1, MyoD, and Mef2C) was downregulated at this time as well. At 15 DPI Atrogin-1 and MuRF-1 were downregulated though upregulation of myogenic markers did not occur. Our results indicate influenza infection is associated with muscle-localized inflammation, protein degradation, and atrophy that is resolved by day 15 post infection. It is known that influenza infection in the elderly leads to increased disability and loss of independence; it is likely muscle atrophy is a contributing factor.