Relative contribution of non-structural protein 1 in dengue pathogenesis
Relative contribution of non-structural protein 1 in dengue pathogenesis
Abstract Dengue is a major public health concern in the tropical and sub-tropical world with no effective treatment. The controversial live attenuated virus vaccine Dengvaxia has boosted the pursuit of sub-unit vaccine approaches, and the non-structural protein 1 (NS1) has recently emerged as a promising candidate. However, we found that NS1 immunization or passive transfer of NS1 antibodies failed to confer protection in symptomatic dengue mouse models using two non mouse-adapted DENV2 strains from the Cosmopolitan genotype that currently circulates in South-East Asia. Furthermore, exogenous administration of purified NS1 did not worsen in vivo vascular leakage in sub-lethally infected mice, thereby supporting that NS1 does not play a critical role in the pathogenesis of these DENV2 strains. Virus chimerization approaches indicated that the prME structural region, but not NS1, plays a critical role in driving in vivo fitness and virulence of the virus, through induction of key pro-inflammatory cytokines. This work highlights that the pathogenic role of NS1 is DENV strain-dependent, which warrants re-evaluation of NS1 as a universal dengue vaccine candidate.
Lee Pei Xuan、Boey Clement Peng Hee、Ong Li Ching、Hapuarachchi Chanditha、Tan Eunice Tze Xin、Alonso Sylvie、Ting Donald Heng Rong、Chia Janice Zuo Hui、Chua Yen Leong、Ng Lee Ching
Department of Microbiology & Immunology, Yong Loo Lin School of Medicine, National University of Singapore||Immunology Programme, Life Sciences Institute, National University of SingaporeDepartment of Microbiology & Immunology, Yong Loo Lin School of Medicine, National University of Singapore||Immunology Programme, Life Sciences Institute, National University of SingaporeDepartment of Microbiology & Immunology, Yong Loo Lin School of Medicine, National University of Singapore||Immunology Programme, Life Sciences Institute, National University of SingaporeEnvironmental Health Institute at National Environment AgencyDepartment of Microbiology & Immunology, Yong Loo Lin School of Medicine, National University of Singapore||Immunology Programme, Life Sciences Institute, National University of SingaporeDepartment of Microbiology & Immunology, Yong Loo Lin School of Medicine, National University of Singapore||Immunology Programme, Life Sciences Institute, National University of SingaporeDepartment of Microbiology & Immunology, Yong Loo Lin School of Medicine, National University of Singapore||Immunology Programme, Life Sciences Institute, National University of SingaporeDepartment of Microbiology & Immunology, Yong Loo Lin School of Medicine, National University of Singapore||Immunology Programme, Life Sciences Institute, National University of SingaporeDepartment of Microbiology & Immunology, Yong Loo Lin School of Medicine, National University of SingaporeEnvironmental Health Institute at National Environment Agency
基础医学生物科学研究方法、生物科学研究技术微生物学
DengueNS1prMEvascular leakage
Lee Pei Xuan,Boey Clement Peng Hee,Ong Li Ching,Hapuarachchi Chanditha,Tan Eunice Tze Xin,Alonso Sylvie,Ting Donald Heng Rong,Chia Janice Zuo Hui,Chua Yen Leong,Ng Lee Ching.Relative contribution of non-structural protein 1 in dengue pathogenesis[EB/OL].(2025-03-28)[2025-05-17].https://www.biorxiv.org/content/10.1101/2020.02.01.929885.点此复制
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