Zika virus protease induces caspase-independent pyroptotic cell death by directly cleaving gasdermin D

Yutaro Yamaoka; Satoko Matsunaga; Sundararaj Stanleyraj Jeremiah; Mayuko Nishi; Kei Miyakawa; Takeshi Morita; Hajera Khatun; Hideaki Shimizu; Nobuhiko Okabe; Hirokazu Kimura; Hideki Hasegawa; Akihide Ryo

doi:10.1016/j.bbrc.2020.11.023

Zika virus protease induces caspase-independent pyroptotic cell death by directly cleaving gasdermin D

Yutaro Yamaoka, Satoko Matsunaga, Sundararaj Stanleyraj Jeremiah, Mayuko Nishi, Kei Miyakawa, Takeshi Morita, Hajera Khatun, Hideaki Shimizu, Nobuhiko Okabe, Hirokazu Kimura, Hideki Hasegawa, Akihide Ryo

Yokohama City University

Research output: Contribution to journal › Article › peer-review

Abstract

The association of Zika virus (ZIKV) infection with a congenital malformation in fetuses, neurological, and other systemic complications in adults have brought significant global health emergency. ZIKV targets nerve cells in the brain and causes cell death, such as pyroptosis, leading to neuroinflammation. Here we described a novel mechanism of pyroptosis caused by ZIKV protease. We found that ZIKV protease directly cleaved the GSDMD into N-terminal fragment (1–249) leading to pyroptosis in a caspase-independent manner, suggesting a direct mechanism of ZIKV-induced cell death and subsequent inflammation. Our findings might shed new light to explore the pathogenesis of ZIKV infections where ZIKV protease might be a suitable target for the development of antiviral agents.

Original language	English
Pages (from-to)	666-671
Number of pages	6
Journal	Biochemical and Biophysical Research Communications
Volume	534
DOIs	https://doi.org/10.1016/j.bbrc.2020.11.023
Publication status	Published - 1 Jan 2021

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10.1016/j.bbrc.2020.11.023

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Yamaoka, Y., Matsunaga, S., Jeremiah, S. S., Nishi, M., Miyakawa, K., Morita, T., Khatun, H., Shimizu, H., Okabe, N., Kimura, H., Hasegawa, H., & Ryo, A. (2021). Zika virus protease induces caspase-independent pyroptotic cell death by directly cleaving gasdermin D. Biochemical and Biophysical Research Communications, 534, 666-671. https://doi.org/10.1016/j.bbrc.2020.11.023

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title = "Zika virus protease induces caspase-independent pyroptotic cell death by directly cleaving gasdermin D",

abstract = "The association of Zika virus (ZIKV) infection with a congenital malformation in fetuses, neurological, and other systemic complications in adults have brought significant global health emergency. ZIKV targets nerve cells in the brain and causes cell death, such as pyroptosis, leading to neuroinflammation. Here we described a novel mechanism of pyroptosis caused by ZIKV protease. We found that ZIKV protease directly cleaved the GSDMD into N-terminal fragment (1–249) leading to pyroptosis in a caspase-independent manner, suggesting a direct mechanism of ZIKV-induced cell death and subsequent inflammation. Our findings might shed new light to explore the pathogenesis of ZIKV infections where ZIKV protease might be a suitable target for the development of antiviral agents.",

author = "Yutaro Yamaoka and Satoko Matsunaga and Jeremiah, {Sundararaj Stanleyraj} and Mayuko Nishi and Kei Miyakawa and Takeshi Morita and Hajera Khatun and Hideaki Shimizu and Nobuhiko Okabe and Hirokazu Kimura and Hideki Hasegawa and Akihide Ryo",

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year = "2021",

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doi = "10.1016/j.bbrc.2020.11.023",

language = "English",

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T1 - Zika virus protease induces caspase-independent pyroptotic cell death by directly cleaving gasdermin D

AU - Yamaoka, Yutaro

AU - Matsunaga, Satoko

AU - Jeremiah, Sundararaj Stanleyraj

AU - Nishi, Mayuko

AU - Miyakawa, Kei

AU - Morita, Takeshi

AU - Khatun, Hajera

AU - Shimizu, Hideaki

AU - Okabe, Nobuhiko

AU - Kimura, Hirokazu

AU - Hasegawa, Hideki

AU - Ryo, Akihide

PY - 2021/1/1

Y1 - 2021/1/1

N2 - The association of Zika virus (ZIKV) infection with a congenital malformation in fetuses, neurological, and other systemic complications in adults have brought significant global health emergency. ZIKV targets nerve cells in the brain and causes cell death, such as pyroptosis, leading to neuroinflammation. Here we described a novel mechanism of pyroptosis caused by ZIKV protease. We found that ZIKV protease directly cleaved the GSDMD into N-terminal fragment (1–249) leading to pyroptosis in a caspase-independent manner, suggesting a direct mechanism of ZIKV-induced cell death and subsequent inflammation. Our findings might shed new light to explore the pathogenesis of ZIKV infections where ZIKV protease might be a suitable target for the development of antiviral agents.

AB - The association of Zika virus (ZIKV) infection with a congenital malformation in fetuses, neurological, and other systemic complications in adults have brought significant global health emergency. ZIKV targets nerve cells in the brain and causes cell death, such as pyroptosis, leading to neuroinflammation. Here we described a novel mechanism of pyroptosis caused by ZIKV protease. We found that ZIKV protease directly cleaved the GSDMD into N-terminal fragment (1–249) leading to pyroptosis in a caspase-independent manner, suggesting a direct mechanism of ZIKV-induced cell death and subsequent inflammation. Our findings might shed new light to explore the pathogenesis of ZIKV infections where ZIKV protease might be a suitable target for the development of antiviral agents.

UR - https://doi.org/10.1016/j.bbrc.2020.11.023

U2 - 10.1016/j.bbrc.2020.11.023

DO - 10.1016/j.bbrc.2020.11.023

M3 - Article

SN - 0006-291X

VL - 534

SP - 666

EP - 671

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

ER -

Zika virus protease induces caspase-independent pyroptotic cell death by directly cleaving gasdermin D

Abstract

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