The RNA Sensor RIG-I Dually Functions as an Innate Sensor and Direct Antiviral Factor for Hepatitis B Virus

Seiichi Sato; Kai Li; Takeshi Kameyama; Takaya Hayashi; Yuji Ishida; Shuko Murakami; Tsunamasa Watanabe; Sayuki Iijima; Yu Sakurai; Koichi Watashi; Susumu Tsutsumi; Yusuke Sato; Hidetaka Akita; Takaji Wakita; Charles M. Rice; Hideyoshi Harashima; Michinori Kohara; Yasuhito Tanaka; Akinori Takaoka

doi:10.1016/j.immuni.2014.12.016

The RNA Sensor RIG-I Dually Functions as an Innate Sensor and Direct Antiviral Factor for Hepatitis B Virus

Seiichi Sato
, Kai Li
, Takeshi Kameyama
, Takaya Hayashi
, Yuji Ishida
, Shuko Murakami
, Tsunamasa Watanabe
, Sayuki Iijima
, Yu Sakurai
, Koichi Watashi
, Susumu Tsutsumi
, Yusuke Sato
, Hidetaka Akita
, Takaji Wakita
, Charles M. Rice
, Hideyoshi Harashima
, Michinori Kohara
, Yasuhito Tanaka
, Akinori Takaoka^*

^*Corresponding author for this work

Hokkaido University
PhoenixBio Co., Ltd.
Nagoya City University
National Institute of Infectious Diseases
Rockefeller University
Tokyo Metropolitan Institute of Medical Science

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

394 Scopus citations

Abstract

Host innate recognition triggers key immune responses for viral elimination. The sensing mechanism of hepatitis B virus (HBV), a DNA virus, and the subsequent downstream signaling events remain to be fully clarified. Here we found that type III but nottype I interferons are predominantly induced in human primary hepatocytes in response to HBV infection, through retinoic acid-inducible gene-I (RIG-I)-mediated sensing of the 5'-ε region of HBV pregenomic RNA. In addition, RIG-I could also counteract the interaction of HBV polymerase (P protein) with the 5'-ε region in an RNA-binding dependent manner, which consistently suppressed viral replication. Liposome-mediated delivery and vector-based expression of this ε region-derived RNA in liver abolished the HBV replication in human hepatocyte-chimeric mice. These findings identify an innate-recognition mechanism by which RIG-I dually functions as an HBV sensor activating innate signaling and to counteract viral polymerase in human hepatocytes.

Original language	English
Pages (from-to)	123-132
Number of pages	10
Journal	Immunity
Volume	42
Issue number	1
DOIs	https://doi.org/10.1016/j.immuni.2014.12.016
State	Published - 20 Jan 2015
Externally published	Yes

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SDG 3 Good Health and Well-being

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10.1016/j.immuni.2014.12.016

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Sato, S., Li, K., Kameyama, T., Hayashi, T., Ishida, Y., Murakami, S., Watanabe, T., Iijima, S., Sakurai, Y., Watashi, K., Tsutsumi, S., Sato, Y., Akita, H., Wakita, T., Rice, C. M., Harashima, H., Kohara, M., Tanaka, Y., & Takaoka, A. (2015). The RNA Sensor RIG-I Dually Functions as an Innate Sensor and Direct Antiviral Factor for Hepatitis B Virus. Immunity, 42(1), 123-132. https://doi.org/10.1016/j.immuni.2014.12.016

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title = "The RNA Sensor RIG-I Dually Functions as an Innate Sensor and Direct Antiviral Factor for Hepatitis B Virus",

abstract = "Host innate recognition triggers key immune responses for viral elimination. The sensing mechanism of hepatitis B virus (HBV), a DNA virus, and the subsequent downstream signaling events remain to be fully clarified. Here we found that type III but nottype I interferons are predominantly induced in human primary hepatocytes in response to HBV infection, through retinoic acid-inducible gene-I (RIG-I)-mediated sensing of the 5'-ε region of HBV pregenomic RNA. In addition, RIG-I could also counteract the interaction of HBV polymerase (P protein) with the 5'-ε region in an RNA-binding dependent manner, which consistently suppressed viral replication. Liposome-mediated delivery and vector-based expression of this ε region-derived RNA in liver abolished the HBV replication in human hepatocyte-chimeric mice. These findings identify an innate-recognition mechanism by which RIG-I dually functions as an HBV sensor activating innate signaling and to counteract viral polymerase in human hepatocytes.",

author = "Seiichi Sato and Kai Li and Takeshi Kameyama and Takaya Hayashi and Yuji Ishida and Shuko Murakami and Tsunamasa Watanabe and Sayuki Iijima and Yu Sakurai and Koichi Watashi and Susumu Tsutsumi and Yusuke Sato and Hidetaka Akita and Takaji Wakita and Rice, \{Charles M.\} and Hideyoshi Harashima and Michinori Kohara and Yasuhito Tanaka and Akinori Takaoka",

note = "Publisher Copyright: {\textcopyright} 2015 Elsevier Inc.",

year = "2015",

month = jan,

day = "20",

doi = "10.1016/j.immuni.2014.12.016",

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Sato, S, Li, K, Kameyama, T, Hayashi, T, Ishida, Y, Murakami, S, Watanabe, T, Iijima, S, Sakurai, Y, Watashi, K, Tsutsumi, S, Sato, Y, Akita, H, Wakita, T, Rice, CM, Harashima, H, Kohara, M, Tanaka, Y & Takaoka, A 2015, 'The RNA Sensor RIG-I Dually Functions as an Innate Sensor and Direct Antiviral Factor for Hepatitis B Virus', Immunity, vol. 42, no. 1, pp. 123-132. https://doi.org/10.1016/j.immuni.2014.12.016

TY - JOUR

T1 - The RNA Sensor RIG-I Dually Functions as an Innate Sensor and Direct Antiviral Factor for Hepatitis B Virus

AU - Sato, Seiichi

AU - Li, Kai

AU - Kameyama, Takeshi

AU - Hayashi, Takaya

AU - Ishida, Yuji

AU - Murakami, Shuko

AU - Watanabe, Tsunamasa

AU - Iijima, Sayuki

AU - Sakurai, Yu

AU - Watashi, Koichi

AU - Tsutsumi, Susumu

AU - Sato, Yusuke

AU - Akita, Hidetaka

AU - Wakita, Takaji

AU - Rice, Charles M.

AU - Harashima, Hideyoshi

AU - Kohara, Michinori

AU - Tanaka, Yasuhito

AU - Takaoka, Akinori

PY - 2015/1/20

Y1 - 2015/1/20

N2 - Host innate recognition triggers key immune responses for viral elimination. The sensing mechanism of hepatitis B virus (HBV), a DNA virus, and the subsequent downstream signaling events remain to be fully clarified. Here we found that type III but nottype I interferons are predominantly induced in human primary hepatocytes in response to HBV infection, through retinoic acid-inducible gene-I (RIG-I)-mediated sensing of the 5'-ε region of HBV pregenomic RNA. In addition, RIG-I could also counteract the interaction of HBV polymerase (P protein) with the 5'-ε region in an RNA-binding dependent manner, which consistently suppressed viral replication. Liposome-mediated delivery and vector-based expression of this ε region-derived RNA in liver abolished the HBV replication in human hepatocyte-chimeric mice. These findings identify an innate-recognition mechanism by which RIG-I dually functions as an HBV sensor activating innate signaling and to counteract viral polymerase in human hepatocytes.

AB - Host innate recognition triggers key immune responses for viral elimination. The sensing mechanism of hepatitis B virus (HBV), a DNA virus, and the subsequent downstream signaling events remain to be fully clarified. Here we found that type III but nottype I interferons are predominantly induced in human primary hepatocytes in response to HBV infection, through retinoic acid-inducible gene-I (RIG-I)-mediated sensing of the 5'-ε region of HBV pregenomic RNA. In addition, RIG-I could also counteract the interaction of HBV polymerase (P protein) with the 5'-ε region in an RNA-binding dependent manner, which consistently suppressed viral replication. Liposome-mediated delivery and vector-based expression of this ε region-derived RNA in liver abolished the HBV replication in human hepatocyte-chimeric mice. These findings identify an innate-recognition mechanism by which RIG-I dually functions as an HBV sensor activating innate signaling and to counteract viral polymerase in human hepatocytes.

UR - https://www.scopus.com/pages/publications/84921280194

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DO - 10.1016/j.immuni.2014.12.016

M3 - 文章

C2 - 25557055

AN - SCOPUS:84921280194

SN - 1074-7613

VL - 42

SP - 123

EP - 132

JO - Immunity

JF - Immunity

IS - 1

ER -

The RNA Sensor RIG-I Dually Functions as an Innate Sensor and Direct Antiviral Factor for Hepatitis B Virus

Abstract

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