Efficient inhibition of hepatitis B virus infection by acylated peptides derived from the large viral surface protein.

作者: Philippe Gripon , Isabelle Cannie , Stephan Urban

DOI: 10.1128/JVI.79.3.1613-1622.2005

关键词:

摘要: The lack of an appropriate in vitro infection system for the major human pathogen hepatitis B virus (HBV) has prevented a molecular understanding early events HBV. We used novel HBV-infectible cell line HepaRG and primary hepatocytes to investigate interference by HBV envelope protein-derived peptides. found that peptide consisting authentically myristoylated N-terminal 47 amino acids pre-S1 domain large viral protein (L protein) specifically infection, with 50% inhibitory concentration (IC50) 8 nM. replacement myristic acid other hydrophobic moieties resulted changes activity, most notably decrease IC50 picomolar concentrations longer unbranched fatty acids. obstruction susceptibility after short preincubation times peptides suggested efficiently target inactivate receptor at hepatocyte surface. Our data both shed light on mechanism entry into provide basis development potent hepadnaviral inhibitors as therapeutic concept treatment Beta.

参考文章(32)
CM Chang, KING-SONG Jeng, Ch-P Hu, SJ Lo, TSUNG-SHENG Su, LP Ting, CHENG-KUNG Chou, SH Han, E Pfaff, J Salfeld, None, Production of hepatitis B virus in vitro by transient expression of cloned HBV DNA in a hepatoma cell line. The EMBO Journal. ,vol. 6, pp. 675- 680 ,(1987) , 10.1002/J.1460-2075.1987.TB04807.X
P Gripon, C Diot, N Thézé, I Fourel, O Loreal, C Brechot, C Guguen-Guillouzo, Hepatitis B virus infection of adult human hepatocytes cultured in the presence of dimethyl sulfoxide. Journal of Virology. ,vol. 62, pp. 4136- 4143 ,(1988) , 10.1128/JVI.62.11.4136-4143.1988
P. Gripon, S. Rumin, S. Urban, J. Le Seyec, D. Glaise, I. Cannie, C. Guyomard, J. Lucas, C. Trepo, C. Guguen-Guillouzo, Infection of a human hepatoma cell line by hepatitis B virus Proceedings of the National Academy of Sciences of the United States of America. ,vol. 99, pp. 15655- 15660 ,(2002) , 10.1073/PNAS.232137699
J. Le Seyec, P. Chouteau, I. Cannie, C. Guguen-Guillouzo, P. Gripon, Role of the Pre-S2 Domain of the Large Envelope Protein in Hepatitis B Virus Assembly and Infectivity Journal of Virology. ,vol. 72, pp. 5573- 5578 ,(1998) , 10.1128/JVI.72.7.5573-5578.1998
Cheol-Young Maeng, Chun Jeih Ryu, Philippe Gripon, Christiane Guguen-Guillouzo, Hyo Jeong Hong, Fine Mapping of Virus-Neutralizing Epitopes on Hepatitis B Virus PreS1 Virology. ,vol. 270, pp. 9- 16 ,(2000) , 10.1006/VIRO.2000.0250
V. Bruss, D. Ganem, The role of envelope proteins in hepatitis B virus assembly Proceedings of the National Academy of Sciences of the United States of America. ,vol. 88, pp. 1059- 1063 ,(1991) , 10.1073/PNAS.88.3.1059
Andreas Berting a,, Christian Fischer, Stephan Schaefer, Wolfgang Garten, Hans-Dieter Klenk, Wolfram H Gerlich, Hemifusion activity of a chimeric influenza virus hemagglutinin with a putative fusion peptide from hepatitis B virus. Virus Research. ,vol. 68, pp. 35- 49 ,(2000) , 10.1016/S0168-1702(00)00150-7
Chun Jeih Ryu, Philippe Gripon, Heung Rok Park, Sung Sup Park, Youn Kyu Kim, Christiane Guguen-Guillouzo, Ook Joon Yoo, Hyo Jeong Hong, In vitro neutralization of hepatitis B virus by monoclonal antibodies against the viral surface antigen Journal of Medical Virology. ,vol. 52, pp. 226- 233 ,(1997) , 10.1002/(SICI)1096-9071(199706)52:2<226::AID-JMV18>3.0.CO;2-I