Liver-expressed Cd302 and Cr1l limit hepatitis C virus cross-species transmission to mice

被引：24

作者：

Brown, Richard J. P. ^{[1
,2
]}

Tegtmeyer, Birthe ^{[2
]}

Sheldon, Julie ^{[2
]}

Khera, Tanvi ^{[2
,3
]}

Anggakusuma ^{[2
,4
]}

Todt, Daniel ^{[2
,5
,6
]}

Vieyres, Gabrielle ^{[2
,7
]}

Weller, Romy ^{[2
]}

Joecks, Sebastian ^{[2
]}

Zhang, Yudi ^{[2
]}

Sake, Svenja ^{[2
]}

Bankwitz, Dorothea ^{[2
]}

Welsch, Kathrin ^{[2
]}

Ginkel, Corinne ^{[2
]}

Engelmann, Michael ^{[2
,5
]}

Gerold, Gisa ^{[8
,9
,10
]}

Steinmann, Eike ^{[2
,5
]}

Yuan, Qinggong ^{[11
,12
]}

Ott, Michael ^{[11
,12
]}

Vondran, Florian W. R. ^{[13
,14
]}

Krey, Thomas ^{[14
,15
,16
,17
,18
]}

Stroeh, Luisa J. ^{[15
]}

Miskey, Csaba ^{[19
]}

Ivics, Zoltan ^{[19
]}

Herder, Vanessa ^{[20
]}

Baumgaertner, Wolfgang ^{[20
]}

Lauber, Chris ^{[2
,21
]}

Seifert, Michael ^{[21
]}

Tarr, Alexander W. ^{[22
,23
,24
]}

McClure, C. Patrick ^{[22
,23
,24
]}

Randall, Glenn ^{[25
]}

Baktash, Yasmine ^{[26
]}

Ploss, Alexander ^{[27
]}

Thi, Viet Loan Dao ^{[28
,29
]}

Michailidis, Eleftherios ^{[29
]}

Saeed, Mohsan ^{[28
,30
]}

Verhoye, Lieven ^{[31
]}

Meuleman, Philip ^{[31
]}

Goedecke, Natascha ^{[32
]}

Wirth, Dagmar ^{[32
,33
]}

Rice, Charles M. ^{[28
]}

Pietschmann, Thomas ^{[2
,14
,16
]}

机构：

[1] Paul Ehrlich Inst, Div Vet Med, D-63225 Langen, Germany

[2] Ctr Expt & Clin Infect Res, Inst Expt Virol, Feodor Lynen Str 7, D-30625 Hannover, Germany

[3] Univ Duisburg Essen, Univ Hosp Essen, Fac Med, Dept Gastroenterol & Hepatol, D-45147 Essen, Germany

[4] UniQure Biopharma BV, Dept Res & Dev, Amsterdam, Netherlands

[5] Ruhr Univ Bochum, Fac Med, Dept Mol & Med Virol, Bochum, Germany

[6] European Virus Bioinformat Ctr EVBC, D-07743 Jena, Germany

[7] Leibniz Inst Expt Virol, Heinrich Pette Inst, Hamburg, Germany

[8] Univ Vet Med Hannover, Dept Physiol Chem, Bunteweg 17, D-30559 Hannover, Germany

[9] Umea Univ, Dept Clin Microbiol, Virol, S-90185 Umea, Sweden

[10] Umea Univ, Wallenberg Ctr Mol Med WCMM, S-90185 Umea, Sweden

[11] Hannover Med Sch, Dept Gastroenterol Hepatol & Endocrinol, D-30625 Hannover, Germany

[12] Twincore Ctr Expt & Clin Infect Res, Feodor Lynen Str 7, D-30625 Hannover, Germany

[13] Hannover Med Sch, Dept Gen Visceral & Transplant Surg, D-30625 Hannover, Germany

[14] German Ctr Infect Res DZIF, Hannover Braunschweig Site, Braunschweig, Germany

[15] Hannover Med Sch, Inst Virol, Hannover, Germany

[16] Hannover Med Sch, Cluster Excellence RESIST EXC 2155, Carl Neuberg Str 1, D-30625 Hannover, Germany

[17] Univ Lubeck, Ctr Struct & Cell Biol Med, Inst Biochem, Lubeck, Germany

[18] Ctr Struct Syst Biol CSSB, Hamburg, Germany

[19] Paul Ehrlich Inst, Div Med Biotechnol, D-63225 Langen, Germany

[20] Univ Vet Med Hannover, Dept Pathol, D-30559 Hannover, Germany

[21] Tech Univ Dresden, Carl Gustav Carus Fac Med, Inst Med Informat & Biometry, Dresden, Germany

[22] Univ Nottingham, Fac Med & Hlth Sci, Sch Life Sci, Nottingham, England

[23] Univ Nottingham, Sch Life Sci, Nottingham, England

[24] Univ Nottingham, NIHR Nottingham BRC, Nottingham, England

[25] Univ Chicago, Dept Microbiol, Chicago, IL 60439 USA

[26] Inst Biol Integrat Sistemas I2SysBio, Parc Cient Barcelona, Valencia 46980, Spain

[27] Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA

[28] Rockefeller Univ, Lab Virol & Infect Dis, New York, NY 10065 USA

[29] Heidelberg Univ Hosp, Schaller Res Grp, Cluster Excellence CellNetworks, Mol Virol,Dept Infect Dis, Heidelberg, Germany

[30] Boston Univ, Sch Med, Dept Biochem, Natl Emerging Infect Dis Labs, Boston, MA 02118 USA

[31] Univ Ghent, Lab Liver Infect Dis, Ghent, Belgium

[32] Helmholtz Ctr Infect Res, Div Model Syst Infect & Immun, Inhoffenstr 7, D-38124 Braunschweig, Germany

[33] Hannover Med Sch, Dept Expt Hematol, D-30625 Hannover, Germany

来源：

SCIENCE ADVANCES | 2020年 / 6卷 / 45期

基金：

欧洲研究理事会;

关键词：

RECEPTOR; REPLICATION; REVEALS; GROWTH; ROLES; ENTRY;

D O I：

10.1126/sciadv.abd3233

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：

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.

引用

页数：18

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