Poultry Science (Sep 2022)
The substitution at residue 218 of the NS5 protein methyltransferase domain of Tembusu virus impairs viral replication and translation and may triggers RIG-I-like receptor signaling
- Xuedong Wu,
- Yuhong Pan,
- Juan Huang,
- Shanzhi Huang,
- Mingshu Wang,
- Shun Chen,
- Mafeng Liu,
- Dekang Zhu,
- Xinxin Zhao,
- Ying Wu,
- Qiao Yang,
- Shaqiu Zhang,
- Xumin Ou,
- Ling Zhang,
- Yunya Liu,
- Yanling Yu,
- Qun Gao,
- Sai Mao,
- Di Sun,
- Bin Tian,
- Zhongqiong Yin,
- Bo Jing,
- Anchun Cheng,
- Renyong Jia
Affiliations
- Xuedong Wu
- Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan Province, 611130, China; Institute of Preventive Veterinary Medicine, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan Province, 611130, China
- Yuhong Pan
- Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan Province, 611130, China; Institute of Preventive Veterinary Medicine, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan Province, 611130, China
- Juan Huang
- Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan Province, 611130, China; Institute of Preventive Veterinary Medicine, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan Province, 611130, China
- Shanzhi Huang
- Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan Province, 611130, China; Institute of Preventive Veterinary Medicine, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan Province, 611130, China
- Mingshu Wang
- Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan Province, 611130, China; Institute of Preventive Veterinary Medicine, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan Province, 611130, China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu City, Sichuan Province, 611130, China
- Shun Chen
- Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan Province, 611130, China; Institute of Preventive Veterinary Medicine, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan Province, 611130, China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu City, Sichuan Province, 611130, China
- Mafeng Liu
- Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan Province, 611130, China; Institute of Preventive Veterinary Medicine, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan Province, 611130, China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu City, Sichuan Province, 611130, China
- Dekang Zhu
- Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan Province, 611130, China; Institute of Preventive Veterinary Medicine, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan Province, 611130, China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu City, Sichuan Province, 611130, China
- Xinxin Zhao
- Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan Province, 611130, China; Institute of Preventive Veterinary Medicine, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan Province, 611130, China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu City, Sichuan Province, 611130, China
- Ying Wu
- Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan Province, 611130, China; Institute of Preventive Veterinary Medicine, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan Province, 611130, China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu City, Sichuan Province, 611130, China
- Qiao Yang
- Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan Province, 611130, China; Institute of Preventive Veterinary Medicine, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan Province, 611130, China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu City, Sichuan Province, 611130, China
- Shaqiu Zhang
- Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan Province, 611130, China; Institute of Preventive Veterinary Medicine, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan Province, 611130, China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu City, Sichuan Province, 611130, China
- Xumin Ou
- Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan Province, 611130, China; Institute of Preventive Veterinary Medicine, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan Province, 611130, China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu City, Sichuan Province, 611130, China
- Ling Zhang
- Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan Province, 611130, China; Institute of Preventive Veterinary Medicine, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan Province, 611130, China
- Yunya Liu
- Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan Province, 611130, China; Institute of Preventive Veterinary Medicine, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan Province, 611130, China
- Yanling Yu
- Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan Province, 611130, China; Institute of Preventive Veterinary Medicine, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan Province, 611130, China
- Qun Gao
- Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan Province, 611130, China; Institute of Preventive Veterinary Medicine, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan Province, 611130, China
- Sai Mao
- Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan Province, 611130, China; Institute of Preventive Veterinary Medicine, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan Province, 611130, China
- Di Sun
- Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan Province, 611130, China; Institute of Preventive Veterinary Medicine, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan Province, 611130, China
- Bin Tian
- Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan Province, 611130, China; Institute of Preventive Veterinary Medicine, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan Province, 611130, China
- Zhongqiong Yin
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu City, Sichuan Province, 611130, China
- Bo Jing
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu City, Sichuan Province, 611130, China
- Anchun Cheng
- Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan Province, 611130, China; Institute of Preventive Veterinary Medicine, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan Province, 611130, China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu City, Sichuan Province, 611130, China
- Renyong Jia
- Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan Province, 611130, China; Institute of Preventive Veterinary Medicine, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan Province, 611130, China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu City, Sichuan Province, 611130, China; Corresponding author:
- Journal volume & issue
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Vol. 101,
no. 9
p. 102017
Abstract
ABSTRACT: Flavivirus RNA cap-methylation plays an important role in viral infection, proliferation, and escape from innate immunity. The methyltransferase (MTase) of the flavivirus NS5 protein catalyzes viral RNA methylation. The E218 amino acid of the NS5 protein MTase domain is one of the active sites of flavivirus methyltransferase. In flaviviruses, the E218A mutation abolished 2’-O methylation activity and significantly reduced N-7 methylation activity. Tembusu virus (TMUV, genus Flavivirus) was a pathogen that caused neurological symptoms in ducklings and decreased egg production in laying ducks. In this study, we focused on a comprehensive understanding of the effects of the E218A mutation on TMUV characteristics and the host immune response. E218A mutation reduced TMUV replication and proliferation, but did not affect viral adsorption and entry. Based on a TMUV replicon system, we found that the E218A mutation impaired viral translation. In addition, E218A mutant virus might be more readily recognized by RIG-I-like receptors to activate the corresponding antiviral immune signaling than WT virus. Together, our data suggest that the E218A mutation of TMUV MTase domain impairs viral replication and translation and may activates RIG-I-like receptor signaling, ultimately leading to a reduction in viral proliferation.
