Double-stranded RNA deaminase ADAR1 promotes the Zika virus replication by inhibiting the activation of protein kinase PKR

Zhou, Suna; Yang, Chia-Han; Zhao, Fengsheng; Huang, Yanxia; Lin, Yuxia; Huang, Chenghui; Ma, Xiaocao; Du, Jingjie; Wang, Yi; Long, Gang; He, Jun; Liu, Chao; Zhang, Ping

doi:10.1074/jbc.ra119.009113

Cited by 36 publications

(40 citation statements)

References 44 publications

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“…ADAR1 limits or controls replication of several viruses, including measles virus, members of Paramyxoviridae family, IAV, HIV-1, vesicular stomatitis virus, and hepatitis delta virus ( Casey, 2012 ; Li et al., 2010 ; Vogel et al., 2020 ; Ward et al., 2011 ; Weiden et al., 2014 ). However, for other viruses, such as Zika and Kaposi's sarcoma-associated herpesvirus, ADAR1 may facilitate replication ( Zhang et al., 2020a ; Zhou et al., 2019 ). It will be interesting for future studies to determine the role of the ADAR1 variants unable to bind Z nucleic acids in these viral infections.…”

Section: Discussionmentioning

confidence: 99%

Adenosine-to-inosine editing of endogenous Z-form RNA by the deaminase ADAR1 prevents spontaneous MAVS-dependent type I interferon responses

et al. 2021

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Section: Discussionmentioning

confidence: 99%

Adenosine-to-inosine editing of endogenous Z-form RNA by the deaminase ADAR1 prevents spontaneous MAVS-dependent type I interferon responses

et al. 2021

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“…ADAR1 also attenuates ORFV inhibition of PKR through the OV20.0 protein and stimulates Zika virus replication in infected cells by inhibiting PKR activation and consequently stimulating Zika viral protein synthesis [174,175].…”

Section: Accepted Articlementioning

confidence: 99%

A tale of two proteins: PACT and PKR and their roles in inflammation

et al. 2021

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“…ADAR1 limits or controls replication of several viruses, including measles virus, members of Paramyxoviridae family, IAV, HIV-1, vesicular stomatitis virus and Hepatitis delta virus (Casey, 2012;Li et al, 2010;Vogel et al, 2020;Ward et al, 2011;Weiden et al, 2014). However, for other viruses such as Zika and KSHV, ADAR1 has been shown to facilitate replication (Zhang et al, 2020a;Zhou et al, 2019). It will be interesting for future studies to determine the role of the ADAR1 variants unable to bind Z nucleic acids in these viral infections.…”

Section: Discussionmentioning

confidence: 99%

Recognition of Z-RNA by ADAR1 limits interferon responses

Tang

Rigby

Young

et al. 2020

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Nucleic acids are powerful triggers of innate immunity and can adopt the unusual Z-conformation. The p150 isoform of adenosine deaminase acting on RNA 1 (ADAR1) prevents aberrant interferon (IFN) induction and contains a Z-nucleic acid binding (Zα) domain. We report that knock-in mice bearing two point mutations in the Zα domain of ADAR1, which abolish binding to Z-form nucleic acids, spontaneously induced type I IFNs and IFN-stimulated genes (ISGs) in multiple organs. This included the lung where both stromal and haematopoietic cells displayed ISG induction in Adar1mZα/mZα mice. Concomitantly, Adar1mZα/mZα mice showed improved control of influenza A virus. The spontaneous IFN response in Adar1mZα/mZα mice required MAVS, implicating cytosolic RNA sensing. Finally, analysis of A-to-I changes revealed a specific requirement of ADAR1’s Zα domain in editing of a subset of RNAs. In summary, our results reveal that endogenous RNAs in Z-conformation have immunostimulatory potential that is curtailed by ADAR1.

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Double-stranded RNA deaminase ADAR1 promotes the Zika virus replication by inhibiting the activation of protein kinase PKR

Cited by 36 publications

References 44 publications

Adenosine-to-inosine editing of endogenous Z-form RNA by the deaminase ADAR1 prevents spontaneous MAVS-dependent type I interferon responses

Adenosine-to-inosine editing of endogenous Z-form RNA by the deaminase ADAR1 prevents spontaneous MAVS-dependent type I interferon responses

A tale of two proteins: PACT and PKR and their roles in inflammation

Recognition of Z-RNA by ADAR1 limits interferon responses

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