MAVS-dependent host species range and pathogenicity of human hepatitis A virus

Asuka Hirai-Yuki; Lucinda Hensley; David R. McGivern; Olga González-López; Anshuman Das; Hui Feng; Lu Sun; Justin E. Wilson; Fengyu Hu; Zongdi Feng; William Lovell; Ichiro Misumi; Jenny P.Y. Ting; Stephanie Montgomery; John Cullen; Jason K. Whitmire; Stanley M. Lemon

doi:10.1126/science.aaf8325

MAVS-dependent host species range and pathogenicity of human hepatitis A virus

Asuka Hirai-Yuki, Lucinda Hensley, David R. McGivern, Olga González-López, Anshuman Das, Hui Feng, Lu Sun, Justin E. Wilson, Fengyu Hu, Zongdi Feng, William Lovell, Ichiro Misumi, Jenny P.Y. Ting, Stephanie Montgomery, John Cullen, Jason K. Whitmire, Stanley M. Lemon

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

81 Scopus citations

Abstract

Hepatotropic viruses are important causes of human disease, but the intrahepatic immune response to hepatitis viruses is poorly understood because of a lack of tractable small-animal models. We describe a murine model of hepatitis A virus (HAV) infection that recapitulates critical features of type A hepatitis in humans. We demonstrate that the capacity of HAV to evade MAVS-mediated type I interferon responses defines its host species range. HAV-induced liver injury was associated with interferon-independent intrinsic hepatocellular apoptosis and hepatic inflammation that unexpectedly resulted from MAVS and IRF3/7 signaling. This murine model thus reveals a previously undefined link between innate immune responses to virus infection and acute liver injury, providing a new paradigm for viral pathogenesis in the liver.

Original language	English (US)
Pages (from-to)	1541-1545
Number of pages	5
Journal	Science
Volume	353
Issue number	6307
DOIs	https://doi.org/10.1126/science.aaf8325
State	Published - Sep 30 2016
Externally published	Yes

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Hirai-Yuki, A., Hensley, L., McGivern, D. R., González-López, O., Das, A., Feng, H., Sun, L., Wilson, J. E., Hu, F., Feng, Z., Lovell, W., Misumi, I., Ting, J. P. Y., Montgomery, S., Cullen, J., Whitmire, J. K., & Lemon, S. M. (2016). MAVS-dependent host species range and pathogenicity of human hepatitis A virus. Science, 353(6307), 1541-1545. https://doi.org/10.1126/science.aaf8325

Hirai-Yuki, A, Hensley, L, McGivern, DR, González-López, O, Das, A, Feng, H, Sun, L, Wilson, JE, Hu, F, Feng, Z, Lovell, W, Misumi, I, Ting, JPY, Montgomery, S, Cullen, J, Whitmire, JK & Lemon, SM 2016, 'MAVS-dependent host species range and pathogenicity of human hepatitis A virus', Science, vol. 353, no. 6307, pp. 1541-1545. https://doi.org/10.1126/science.aaf8325

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title = "MAVS-dependent host species range and pathogenicity of human hepatitis A virus",

abstract = "Hepatotropic viruses are important causes of human disease, but the intrahepatic immune response to hepatitis viruses is poorly understood because of a lack of tractable small-animal models. We describe a murine model of hepatitis A virus (HAV) infection that recapitulates critical features of type A hepatitis in humans. We demonstrate that the capacity of HAV to evade MAVS-mediated type I interferon responses defines its host species range. HAV-induced liver injury was associated with interferon-independent intrinsic hepatocellular apoptosis and hepatic inflammation that unexpectedly resulted from MAVS and IRF3/7 signaling. This murine model thus reveals a previously undefined link between innate immune responses to virus infection and acute liver injury, providing a new paradigm for viral pathogenesis in the liver.",

author = "Asuka Hirai-Yuki and Lucinda Hensley and McGivern, {David R.} and Olga Gonz{\'a}lez-L{\'o}pez and Anshuman Das and Hui Feng and Lu Sun and Wilson, {Justin E.} and Fengyu Hu and Zongdi Feng and William Lovell and Ichiro Misumi and Ting, {Jenny P.Y.} and Stephanie Montgomery and John Cullen and Whitmire, {Jason K.} and Lemon, {Stanley M.}",

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doi = "10.1126/science.aaf8325",

language = "English (US)",

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AU - Hirai-Yuki, Asuka

AU - Hensley, Lucinda

AU - McGivern, David R.

AU - González-López, Olga

AU - Das, Anshuman

AU - Feng, Hui

AU - Sun, Lu

AU - Wilson, Justin E.

AU - Hu, Fengyu

AU - Feng, Zongdi

AU - Lovell, William

AU - Misumi, Ichiro

AU - Ting, Jenny P.Y.

AU - Montgomery, Stephanie

AU - Cullen, John

AU - Whitmire, Jason K.

AU - Lemon, Stanley M.

PY - 2016/9/30

Y1 - 2016/9/30

N2 - Hepatotropic viruses are important causes of human disease, but the intrahepatic immune response to hepatitis viruses is poorly understood because of a lack of tractable small-animal models. We describe a murine model of hepatitis A virus (HAV) infection that recapitulates critical features of type A hepatitis in humans. We demonstrate that the capacity of HAV to evade MAVS-mediated type I interferon responses defines its host species range. HAV-induced liver injury was associated with interferon-independent intrinsic hepatocellular apoptosis and hepatic inflammation that unexpectedly resulted from MAVS and IRF3/7 signaling. This murine model thus reveals a previously undefined link between innate immune responses to virus infection and acute liver injury, providing a new paradigm for viral pathogenesis in the liver.

AB - Hepatotropic viruses are important causes of human disease, but the intrahepatic immune response to hepatitis viruses is poorly understood because of a lack of tractable small-animal models. We describe a murine model of hepatitis A virus (HAV) infection that recapitulates critical features of type A hepatitis in humans. We demonstrate that the capacity of HAV to evade MAVS-mediated type I interferon responses defines its host species range. HAV-induced liver injury was associated with interferon-independent intrinsic hepatocellular apoptosis and hepatic inflammation that unexpectedly resulted from MAVS and IRF3/7 signaling. This murine model thus reveals a previously undefined link between innate immune responses to virus infection and acute liver injury, providing a new paradigm for viral pathogenesis in the liver.

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JF - Science

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MAVS-dependent host species range and pathogenicity of human hepatitis A virus

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