Poultry Science (Dec 2024)
Characterization of duck tembusu virus NS2A membrane topology and functional residues in transmembrane domain-3 on viral proliferation
- Wei Zhang,
- Miao Zeng,
- Bowen Jiang,
- Yao Cheng,
- Yu He,
- Zhen Wu,
- Tao Wang,
- Mingshu Wang,
- Renyong Jia,
- Dekang Zhu,
- Mafeng Liu,
- Xinxin Zhao,
- Qiao Yang,
- Ying Wu,
- Shaqiu Zhang,
- Juan Huang,
- Xumin Ou,
- Di Sun,
- Andres Merits,
- Anchun Cheng,
- Shun Chen
Affiliations
- Wei Zhang
- Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan 611130, China
- Miao Zeng
- Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan 611130, China
- Bowen Jiang
- Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan 611130, China
- Yao Cheng
- Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan 611130, China
- Yu He
- Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan 611130, China; Key Laboratory of Agricultural Bioinformatics of Ministry of Education, Sichuan Agricultural University, Chengdu, Sichuan 611130, China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu, Sichuan 611130, China
- Zhen Wu
- Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan 611130, China; Key Laboratory of Agricultural Bioinformatics of Ministry of Education, Sichuan Agricultural University, Chengdu, Sichuan 611130, China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu, Sichuan 611130, China
- Tao Wang
- Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan 611130, China; Key Laboratory of Agricultural Bioinformatics of Ministry of Education, Sichuan Agricultural University, Chengdu, Sichuan 611130, China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu, Sichuan 611130, China
- Mingshu Wang
- Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan 611130, China; Key Laboratory of Agricultural Bioinformatics of Ministry of Education, Sichuan Agricultural University, Chengdu, Sichuan 611130, China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu, Sichuan 611130, China
- Renyong Jia
- Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan 611130, China; Key Laboratory of Agricultural Bioinformatics of Ministry of Education, Sichuan Agricultural University, Chengdu, Sichuan 611130, China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu, Sichuan 611130, China
- Dekang Zhu
- Key Laboratory of Agricultural Bioinformatics of Ministry of Education, Sichuan Agricultural University, Chengdu, Sichuan 611130, China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu, Sichuan 611130, China
- Mafeng Liu
- Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan 611130, China; Key Laboratory of Agricultural Bioinformatics of Ministry of Education, Sichuan Agricultural University, Chengdu, Sichuan 611130, China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu, Sichuan 611130, China
- Xinxin Zhao
- Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan 611130, China; Key Laboratory of Agricultural Bioinformatics of Ministry of Education, Sichuan Agricultural University, Chengdu, Sichuan 611130, China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu, Sichuan 611130, China
- Qiao Yang
- Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan 611130, China; Key Laboratory of Agricultural Bioinformatics of Ministry of Education, Sichuan Agricultural University, Chengdu, Sichuan 611130, China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu, Sichuan 611130, China
- Ying Wu
- Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan 611130, China; Key Laboratory of Agricultural Bioinformatics of Ministry of Education, Sichuan Agricultural University, Chengdu, Sichuan 611130, China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu, Sichuan 611130, China
- Shaqiu Zhang
- Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan 611130, China; Key Laboratory of Agricultural Bioinformatics of Ministry of Education, Sichuan Agricultural University, Chengdu, Sichuan 611130, China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu, Sichuan 611130, China
- Juan Huang
- Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan 611130, China; Key Laboratory of Agricultural Bioinformatics of Ministry of Education, Sichuan Agricultural University, Chengdu, Sichuan 611130, China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu, Sichuan 611130, China
- Xumin Ou
- Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan 611130, China; Key Laboratory of Agricultural Bioinformatics of Ministry of Education, Sichuan Agricultural University, Chengdu, Sichuan 611130, China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu, Sichuan 611130, China
- Di Sun
- Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan 611130, China; Key Laboratory of Agricultural Bioinformatics of Ministry of Education, Sichuan Agricultural University, Chengdu, Sichuan 611130, China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu, Sichuan 611130, China
- Andres Merits
- Institute of Technology, University of Tartu, Tartu 50090, Estonia
- Anchun Cheng
- Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan 611130, China; Key Laboratory of Agricultural Bioinformatics of Ministry of Education, Sichuan Agricultural University, Chengdu, Sichuan 611130, China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu, Sichuan 611130, China
- Shun Chen
- Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan 611130, China; Key Laboratory of Agricultural Bioinformatics of Ministry of Education, Sichuan Agricultural University, Chengdu, Sichuan 611130, China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu, Sichuan 611130, China; Corresponding author.
- Journal volume & issue
-
Vol. 103,
no. 12
p. 104423
Abstract
Flavivirus nonstructural protein 2A (NS2A) is a small endoplasmic reticulum (ER)-resident, hydrophobic transmembrane protein that function in viral replication, virion assembly and evasion of the host immune response. Despite previous studies on the role of duck Tembusu virus (DTMUV) NS2A in inhibiting the host immune response, its membrane topology has not been clearly addressed (Zhang et al., 2020; Zhang et al., 2022). Here, we present the first report on the membrane topology model and functional characterization of DTMUV NS2A. Our findings demonstrate that DTMUV NS2A localizes to the endoplasmic reticulum (ER) and associates with viral double-stranded RNA, with a single segment (TMD3, amino acids 72 to 95) spanning the ER membrane. To better delineate the residues in NS2A-TMD3 related to viral properties, specific mutations were introduced to generate DTMUV replicons and infectious cDNA clones. Functional analysis indicates that L77, Q86 and L89 of NS2A are crucial for viral RNA synthesis, while residues M79 and F83 are crucial for the assembly or release of viral particles. Moreover, these mutations attenuated the virulence of DTMUV in vivo. Collectively, our results shed light on the relationship between the transmembrane of DTMUV NS2A and its functions in virus proliferation, providing insights for further understanding the molecular mechanisms of NS2A in the virus life cycle.
