Liver-expressed Cd302 and Cr1l limit hepatitis C virus cross-species transmission to mice.
Liver-expressed Cd302 and Cr1l limit hepatitis C virus cross-species transmission to mice.
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DOI：
10.1126/sciadv.abd3233
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发表时间：
2020-11
期刊：
影响因子：
13.6
通讯作者：
Pietschmann T
中科院分区：
文献类型：
--
作者：
Brown RJP;Tegtmeyer B;Sheldon J;Khera T;Anggakusuma;Todt D;Vieyres G;Weller R;Joecks S;Zhang Y;Sake S;Bankwitz D;Welsch K;Ginkel C;Engelmann M;Gerold G;Steinmann E;Yuan Q;Ott M;Vondran FWR;Krey T;Ströh LJ;Miskey C;Ivics Z;Herder V;Baumgärtner W;Lauber C;Seifert M;Tarr AW;McClure CP;Randall G;Baktash Y;Ploss A;Thi VLD;Michailidis E;Saeed M;Verhoye L;Meuleman P;Goedecke N;Wirth D;Rice CM;Pietschmann T
两种跨膜蛋白协同阻断嗜人丙型肝炎病毒感染小鼠肝细胞丙型肝炎病毒（HCV）没有动物宿主，只感染人类。为了研究限制啮齿动物感染的物种屏障决定因素，进行小鼠肝脏互补DNA文库筛选，鉴定跨膜蛋白Cd302和Cr1l作为HCV传播的有效限制因子。联合异位表达在人肝癌细胞中阻碍了HCV的摄取，并协同介导了免疫基因的非经典程序的转录失调。这两种因子在小鼠肝细胞中的表达都是组成性的，并且不是干扰素诱导的，而在小鼠直系同源物和人类对应物之间观察到肝脏表达和限制HCV能力的差异。在人HCV进入因子转基因小鼠中内源性Cd302表达的基因消除增加了肝细胞对适应的HCV株的容许性以及代谢过程和宿主防御基因的表达失调。这些发现突出了人类与小鼠在肝脏内在抗病毒免疫方面的差异，并促进了下一代小鼠模型的开发，用于HCV候选疫苗的临床前测试。
Two transmembrane proteins cooperate to block infection of murine hepatocytes by human-tropic hepatitis C virus. Hepatitis C virus (HCV) has no animal reservoir, infecting only humans. To investigate species barrier determinants limiting infection of rodents, murine liver complementary DNA library screening was performed, identifying transmembrane proteins Cd302 and Cr1l as potent restrictors of HCV propagation. Combined ectopic expression in human hepatoma cells impeded HCV uptake and cooperatively mediated transcriptional dysregulation of a noncanonical program of immunity genes. Murine hepatocyte expression of both factors was constitutive and not interferon inducible, while differences in liver expression and the ability to restrict HCV were observed between the murine orthologs and their human counterparts. Genetic ablation of endogenous Cd302 expression in human HCV entry factor transgenic mice increased hepatocyte permissiveness for an adapted HCV strain and dysregulated expression of metabolic process and host defense genes. These findings highlight human-mouse differences in liver-intrinsic antiviral immunity and facilitate the development of next-generation murine models for preclinical testing of HCV vaccine candidates.
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影响因子：
14.8
作者：
Kelley LA;Mezulis S;Yates CM;Wass MN;Sternberg MJ
通讯作者：
Sternberg MJ
影响因子：
64.8
作者：
Dorner, Marcus;Horwitz, Joshua A.;Robbins, Justin B.;Barry, Walter T.;Feng, Qian;Mu, Kathy;Jones, Christopher T.;Schoggins, John W.;Catanese, Maria Teresa;Burton, Dennis R.;Law, Mansun;Rice, Charles M.;Ploss, Alexander
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Ploss, Alexander
影响因子：
6.7
作者：
Coller KE;Berger KL;Heaton NS;Cooper JD;Yoon R;Randall G
通讯作者：
Randall G
影响因子：
7.6
作者：
Chen, Zhilei;Simeon, Rudo L.;Rice, Charles M.
通讯作者：
Rice, Charles M.
DOI：
10.1073/pnas.82.10.3197
发表时间：
1985-01-01
影响因子：
11.1
作者：
ESKO, JD;STEWART, TE;TAYLOR, WH
通讯作者：
TAYLOR, WH