An RNA-based system to study hepatitis B virus replication and evaluate antivirals

被引:5
作者
Yu, Yingpu [1 ]
Schneider, William M. [1 ]
Kass, Maximilian A. [1 ,2 ]
Michailidis, Eleftherios [1 ,9 ]
Acevedo, Ashley [1 ]
Mosimann, Ana L. Pamplona [1 ,10 ]
Bordignon, Juliano [1 ,10 ]
Koenig, Alexander [3 ]
Livingston, Christine M. [3 ]
van Gijzel, Hardeep [4 ]
Ni, Yi [5 ]
Ambrose, Pradeep M. [1 ,6 ]
Freije, Catherine A. [1 ]
Zhang, Mengyin [1 ]
Zou, Chenhui [1 ,7 ]
Kabbani, Mohammad [1 ,8 ]
Quirk, Corrine [1 ]
Jahan, Cyprien [1 ,11 ]
Wu, Xianfang [1 ,12 ]
Urban, Stephan [2 ,5 ]
You, Shihyun [3 ]
Shlomai, Amir [1 ,13 ,14 ,15 ]
Jong, Ype P. de [1 ,7 ]
Rice, Charles M. [1 ]
机构
[1] Rockefeller Univ, Lab Virol & Infect Dis, New York, NY 10065 USA
[2] Univ Hosp Heidelberg, Dept Infect Dis, Mol Virol, Heidelberg, Germany
[3] GSK, Infect Dis Res Unit, Upper Providence, PA 19426 USA
[4] GSK, Computat Biol, Genome Sci, Stevenage, England
[5] German Ctr Infect Res DZIF, Partner Site Heidelberg, Heidelberg, Germany
[6] Weill Cornell Med, Dept Physiol Biophys & Syst Biol, New York, NY 10065 USA
[7] Weill Cornell Med Coll, Div Gastroenterol & Hepatol, New York, NY 10065 USA
[8] Hannover Med Sch, Dept Gastroenterol Hepatol & Endocrinol, Hannover, Germany
[9] Emory Univ, Dept Pediat, Lab Biochem Pharmacol, Sch Med, Atlanta, GA USA
[10] Fiocruz MS, Inst Carlos Chagas, Curitiba, Brazil
[11] Univ Paris Saclay, Ecole Normale Super Paris Saclay, Dept Biol, Cachan, France
[12] Cleveland Clin Fdn, Lerner Res Inst, Cleveland, OH USA
[13] Tel Aviv Univ, Dept Med D, Tel Aviv, Israel
[14] Tel Aviv Univ, Beilinson Hosp, Liver Inst, Tel Aviv, Israel
[15] Tel Aviv Univ, Fac Med, Tel Aviv, Israel
关键词
PREGENOME; GENOTYPES; SEQUENCE; HBV; DNA;
D O I
10.1126/sciadv.adg6265
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 B virus (HBV) chronically infects an estimated 300 million people, and standard treatments are rarely curative. Infection increases the risk of liver cirrhosis and hepatocellular carcinoma, and consequently, nearly 1 million people die each year from chronic hepatitis B. Tools and approaches that bring insights into HBV biology and facilitate the discovery and evaluation of antiviral drugs are in demand. Here, we describe a method to initiate the replication of HBV, a DNA virus, using synthetic RNA. This approach eliminates contaminating background signals from input virus or plasmid DNA that plagues existing systems and can be used to study multiple stages of HBV replication. We further demonstrate that this method can be uniquely applied to identify sequence variants that confer resistance to antiviral drugs.
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页数:14
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