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

被引：76

作者：

Hirai-Yuki, Asuka ^{[1
,2
]}

Hensley, Lucinda ^{[1
,2
]}

McGivern, David R. ^{[1
,3
]}

Gonzalez-Lopez, Olga ^{[1
,2
]}

Das, Anshuman ^{[1
,2
]}

Feng, Hui ^{[1
,2
]}

Sun, Lu ^{[1
,2
]}

Wilson, Justin E. ^{[1
,2
,4
]}

Hu, Fengyu ^{[1
,2
]}

Feng, Zongdi ^{[1
,2
,7
]}

Lovell, William ^{[1
]}

Misumi, Ichiro ^{[1
,2
,4
]}

Ting, Jenny P. -Y. ^{[1
,2
,4
]}

Montgomery, Stephanie ^{[1
,5
]}

Cullen, John ^{[6
]}

Whitmire, Jason K. ^{[1
,2
,4
]}

Lemon, Stanley M. ^{[1
,2
,3
]}

机构：

[1] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27517 USA

[2] Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC 27517 USA

[3] Univ N Carolina, Dept Med, Chapel Hill, NC 27517 USA

[4] Univ N Carolina, Dept Genet, Chapel Hill, NC 27517 USA

[5] Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC 27517 USA

[6] North Carolina State Univ, Coll Vet Med, Dept Populat Hlth & Pathobiol, Raleigh, NC 27607 USA

[7] Nationwide Childrens Hosp, Res Inst, Ctr Vaccines & Immun, Columbus, OH USA

来源：

SCIENCE | 2016年 / 353卷 / 6307期

关键词：

INTERFERON REGULATORY FACTOR-3; LIVER; INFECTION; APOPTOSIS; UBIQUITINATION; IMMUNITY; PATHWAY; MODELS; IRF-3; DEATH;

D O I：

10.1126/science.aaf8325

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：1541 / 1545

页数：6

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