Secretory pathways and multiple functions of nonstructural protein 1 in flavivirus infection

Senzhao Zhang; Yu He; Zhen Wu; Mingshu Wang; Renyong Jia; Dekang Zhu; Mafeng Liu; Xinxin Zhao; Qiao Yang; Ying Wu; Shaqiu Zhang; Juan Huang; Xumin Ou; Qun Gao; Di Sun; Ling Zhang; Yanling Yu; Shun Chen; Anchun Cheng

doi:10.3389/fimmu.2023.1205002

Secretory pathways and multiple functions of nonstructural protein 1 in flavivirus infection

Front Immunol. 2023 Jul 13:14:1205002. doi: 10.3389/fimmu.2023.1205002. eCollection 2023.

Authors

Senzhao Zhang^{1

2

3}, Yu He^{1

2

3}, Zhen Wu^{1

2

3}, Mingshu Wang^{1

2

3}, Renyong Jia^{1

2

3}, Dekang Zhu^{1

2

3}, Mafeng Liu^{1

2

3}, Xinxin Zhao^{1

2

3}, Qiao Yang^{1

2

3}, Ying Wu^{1

2

3}, Shaqiu Zhang^{1

2

3}, Juan Huang^{1

2

3}, Xumin Ou^{1

2

3}, Qun Gao^{1

2

3}, Di Sun^{1

2

3}, Ling Zhang¹, Yanling Yu¹, Shun Chen^{1

2

3}, Anchun Cheng^{1

2

3}

Affiliations

¹ Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, China.
² Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu, Sichuan, China.
³ Engineering Research Center of Southwest Animal Disease Prevention and Control Technology, Ministry of Education of the People's Republic of China, Chengdu, China.

Abstract

The genus Flavivirus contains a wide variety of viruses that cause severe disease in humans, including dengue virus, yellow fever virus, Zika virus, West Nile virus, Japanese encephalitis virus and tick-borne encephalitis virus. Nonstructural protein 1 (NS1) is a glycoprotein that encodes a 352-amino-acid polypeptide and has a molecular weight of 46-55 kDa depending on its glycosylation status. NS1 is highly conserved among multiple flaviviruses and occurs in distinct forms, including a dimeric form within the endoplasmic reticulum, a cell-associated form on the plasma membrane, or a secreted hexameric form (sNS1) trafficked to the extracellular matrix. Intracellular dimeric NS1 interacts with other NSs to participate in viral replication and virion maturation, while extracellular sNS1 plays a critical role in immune evasion, flavivirus pathogenesis and interactions with natural vectors. In this review, we provide an overview of recent research progress on flavivirus NS1, including research on the structural details, the secretory pathways in mammalian and mosquito cells and the multiple functions in viral replication, immune evasion, pathogenesis and interaction with natural hosts, drawing together the previous data to determine the properties of this protein.

Keywords: flavivirus; host-virus interactions; immune evasion; nonstructural protein 1; pathogenesis; secretory pathways; structure.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Encephalitis Viruses, Tick-Borne*
Flavivirus Infections*
Humans
Mammals
Mosquito Vectors
Secretory Pathway
Zika Virus Infection*
Zika Virus* / metabolism

Grants and funding

This work was funded by grants from the National Key Research and Development Program of China (2022YFD1801900), National Natural Science Foundation of China (32272976), Sichuan Provincial Department of science and technology international scientific and technological innovation cooperation (2022YFH0026), the earmarked fund for China Agriculture Research System (CARS-42-17), and the Program Sichuan Veterinary Medicine and Drug Innovation Group of China Agricultural Research System (SCCXTD-2021-18).