Liu Chenggang, Li Linlin, Dong Jiawen, Zhang Junqin, Huang Yunzhen, Zhai Qi, Xiang Yong, Jin Jin, Huang Xianshe, Wang Gang, Sun Minhua, Liao Ming
Key Laboratory of Livestock Disease Prevention and Treatment of Guangdong Province, Institute of Animal Health, Guangdong Academy of Agricultural Sciences, Guangzhou 510640, China; Key Laboratory for Prevention and Control of Avian Influenza and Other Major Poultry Diseases, Ministry of Agriculture and Rural Affairs, Guangzhou 510640, China; Shanwei Academy of Agricultural Sciences, Shanwei 516699, China.
Key Laboratory of Livestock Disease Prevention and Treatment of Guangdong Province, Institute of Animal Health, Guangdong Academy of Agricultural Sciences, Guangzhou 510640, China; Key Laboratory for Prevention and Control of Avian Influenza and Other Major Poultry Diseases, Ministry of Agriculture and Rural Affairs, Guangzhou 510640, China; Scientific Observation and Experiment Station of Veterinary Drugs and Diagnostic Techniques of Guangdong Province, Ministry of Agriculture and Rural Affairs, Guangzhou 510640, China.
Vet Microbiol. 2023 Apr;279:109677. doi: 10.1016/j.vetmic.2023.109677. Epub 2023 Feb 5.
While blocking inflammation is an effective way to ease the symptoms of gout disease in humans, the treatment and prevention of gout in goslings infected with goose astrovirus (GAstV), a recently emergent condition, remain unclear. In this study, we investigated the reprogramming of the host genes as a result of GAstV infection by combining analysis of the global transcriptome and metabolic network pathways in the kidneys of goslings infected with GAstV. We showed that as GAstV replication increased in vivo, the regulation of key enzymes in the host metabolism progressively increased, flowing metabolites into the purine/pyrimidine biosynthesis pathways. Furthermore, we found that GAstV: 1) inhibits the host oxidation-reduction response by inhibiting the expression of the catalase gene; 2) activates the Toll-like receptor 2 pathway to enhance the immune inflammatory response; and 3) activates the key enzyme in lactic acid synthesis to produce lactate accumulation which inhibits the host's antiviral response, so as to facilitate the replication of the virus itself. This study provided the first insight into the overall metabolic requirements of GAstV for replication in vivo by combining transcriptome with metabolic network pathway information.
虽然阻断炎症是缓解人类痛风疾病症状的有效方法,但对于感染鹅星状病毒(GAstV)的雏鹅(一种最近出现的病症)的痛风治疗和预防仍不清楚。在本研究中,我们通过结合对感染GAstV的雏鹅肾脏中的全局转录组和代谢网络途径的分析,研究了GAstV感染导致的宿主基因重编程。我们发现,随着GAstV在体内复制的增加,宿主代谢中关键酶的调节逐渐增加,使代谢产物流入嘌呤/嘧啶生物合成途径。此外,我们发现GAstV:1)通过抑制过氧化氢酶基因的表达来抑制宿主氧化还原反应;2)激活Toll样受体2途径以增强免疫炎症反应;3)激活乳酸合成中的关键酶以产生乳酸积累,从而抑制宿主的抗病毒反应,以便于病毒自身的复制。本研究通过将转录组与代谢网络途径信息相结合,首次深入了解了GAstV在体内复制的整体代谢需求。