Lipopolysaccharide aggravates canine influenza a (H3N2) virus infection and lung damage via mTOR/autophagy in vivo and in vitro. (February 2023)

• Record Type: Journal Article
• Authors: Wang, Mengmeng; Li, Haolei; Liu, Shuiping; Ge, Lei; Muhmood, Azhar; Liu, Dandan; Gan, Fang; Liu, Yunhuan; Chen, Xingxiang; Huang, Kehe
• Is Part Of: Food and chemical toxicology. Volume 172(2023)
• Publication Date: 2023-02
• Subjects: Canine influenza a (H3N2) virus -- Lipopolysaccharide -- Replication -- mTOR/autophagy; Toxicology -- Periodicals; Food poisoning -- Periodicals; Food Poisoning -- Periodicals; Toxicology -- Periodicals; Toxicologie -- Périodiques; Intoxications alimentaires -- Périodiques; Food poisoning; Toxicology; Periodicals; Electronic journals; 615.9
• DOI: 10.1016/j.fct.2022.113597
• Languages: English
• ISSNs: 0278-6915

Abstract

Abstract: Influenza A (H3N2) accounts for the majority of influenza worldwide and continues to challenge human health. Disturbance in the gut microbiota caused by many diseases leads to increased production of lipopolysaccharide (LPS), and LPS induces sepsis and conditions associated with local or systemic inflammation. However, to date, little attention has been paid to the potential impact of LPS on influenza A (H3N2) infection and the potential mechanism. Hence, in this study we used canine influenza A (H3N2) virus (CIV) as a model of influenza A virus to investigate the effect of low-dose of LPS on CIV replication and lung damage and explore the underlying mechanism in mice and A549 and HPAEpiC cells. The results showed that LPS (25 μg/kg) increased CIV infection and lung damage in mice, as indicated by pulmonary virus titer, viral NP levels, lung index, and pulmonary histopathology. LPS (1 μg/ml) also increased CIV replication in A549 cells as indicated by the above same parameters. Furthermore, low doses of LPS reduced CIV-induced p-mTOR protein expression and enhanced CIV-induced autophagy-related mRNA/protein expressions in vivo and in vitro . In addition, the use of the mTOR activator, MHY1485, reversed CIV-induced autophagy and CIV replication in A549 and HPAEpiC cells, respectively. siATG5 alleviated CIV replication exacerbated by LPS in the two lines. In conclusion, LPS aggravates CIV infection and lung damage via mTOR/autophagy. Graphical abstract: Image 1 Highlights: LPS aggravated CIV-induced viral infection in vivo and in vitro. LPS exacerbated CIV-induced acute lung inflammation and injury in mice. LPS promoted CIV infection via mTOR/autophagy signaling pathway.