An evolutionary NS1 mutation enhances Zika virus evasion of host interferon induction.
Hongjie Xia,Huanle Luo,Chao Shan,Antonio E. Muruato,Bruno Tardelli Diniz Nunes,Bruno Tardelli Diniz Nunes,Daniele Barbosa de Almeida Medeiros,Daniele Barbosa de Almeida Medeiros,Jing Zou,Xuping Xie,Maria Isabel Giraldo,Pedro Fernando da Costa Vasconcelos,Pedro Fernando da Costa Vasconcelos,Scott C. Weaver,Tian Wang,Ricardo Rajsbaum,Pei Yong Shi +16 more
TLDR
The results support the mechanism that ZIKV has accumulated mutation(s) that increases the ability to evade immune response and potentiates infection and epidemics and interferes with interferon production through interaction with TBK1.Abstract:
Virus-host interactions determine an infection outcome. The Asian lineage of Zika virus (ZIKV), responsible for the recent epidemics, has fixed a mutation in the NS1 gene after 2012 that enhances mosquito infection. Here we report that the same mutation confers NS1 to inhibit interferon-β induction. This mutation enables NS1 binding to TBK1 and reduces TBK1 phosphorylation. Engineering the mutation into a pre-epidemic ZIKV strain debilitates the virus for interferon-β induction; reversing the mutation in an epidemic ZIKV strain invigorates the virus for interferon-β induction; these mutational effects are lost in IRF3-knockout cells. Additionally, ZIKV NS2A, NS2B, NS4A, NS4B, and NS5 can also suppress interferon-β production through targeting distinct components of the RIG-I pathway; however, for these proteins, no antagonistic difference is observed among various ZIKV strains. Our results support the mechanism that ZIKV has accumulated mutation(s) that increases the ability to evade immune response and potentiates infection and epidemics.read more
Citations
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Evasion of Type I Interferon by SARS-CoV-2.
Hongjie Xia,Zengguo Cao,Xuping Xie,Xianwen Zhang,John Yun Chung Chen,Hualei Wang,Vineet D. Menachery,Ricardo Rajsbaum,Pei Yong Shi +8 more
TL;DR: Insight is provided on SARS-CoV-2 evasion of IFN-I response and its potential impact on viral transmission and pathogenesis.
Journal ArticleDOI
The continued threat of emerging flaviviruses
TL;DR: The basic biology of these viruses, their life cycles, the diseases they cause and available therapeutic options are reviewed, and the global distribution of flaviviruses is discussed, with a focus on lesser-known species that have the potential to emerge more broadly in human populations.
Journal ArticleDOI
The emergence of Zika virus and its new clinical syndromes.
TL;DR: The rapid development of cell culture and animal models has facilitated a new understanding of ZIKV biology and made it possible to generate multiple ZikV vaccine candidates, which are advancing through clinical trials.
Journal ArticleDOI
Viral Innate Immune Evasion and the Pathogenesis of Emerging RNA Virus Infections
Tessa Nelemans,Marjolein Kikkert +1 more
TL;DR: What is currently known about the role of interferons and host immune evasion in the pathogenesis of emerging coronaviruses, alphavirus and flaviviruses is discussed.
Journal ArticleDOI
Species-specific disruption of STING-dependent antiviral cellular defenses by the Zika virus NS2B3 protease.
Qiang Ding,Jenna M. Gaska,Florian Douam,Lei Wei,David J. Kim,Metodi Balev,Brigitte Heller,Alexander Ploss +7 more
TL;DR: ZIKV efficiently infects fibroblasts from humans, great apes, New and Old World monkeys, but not rodents, and an enzyme shared by many flaviviruses (NS2B3) is responsible for functionally inactivating this antiviral defense.
References
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IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway.
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