Hepatitis C Virus NS2 Protein Serves as a Scaffold for Virus Assembly by Interacting with both Structural and Nonstructural Proteins

作者: Y. Ma , M. Anantpadma , J. M. Timpe , S. Shanmugam , S. M. Singh

DOI: 10.1128/JVI.01070-10

关键词:

摘要: Many aspects of the assembly hepatitis C virus (HCV) remain incompletely understood. To characterize role NS2 in production infectious virus, we determined interaction partners among other HCV proteins during productive infection. Pulldown assays showed that forms complexes with both structural and nonstructural proteins, including E1, E2, p7, NS3, NS5A. Confocal microscopy also demonstrated colocalizes NS5A dot-like structures near lipid droplets. However, did not coprecipitate E2 interacted only weakly NS3 pulldown assays. Also, there was no demonstrable between p7 or such Therefore, is uniquely capable interacting proteins. Among mutations NS2, prevent significantly reduced NS2-mediated protein interactions. These altered intracellular distribution appeared to modulate membrane topology C-terminal domain NS2. results suggest acts coordinate by mediating interactions envelope within replication adjacent droplets, where particle thought occur. may play an accessory regulating topology, which important for therefore function.

参考文章(42)
Bernard B. Allan, William E. Balch, In vitro analysis of endoplasmic-reticulum-to-golgi transport in mammalian cells. Current protocols in pharmacology. ,(1998) , 10.1002/0471143030.CB1103S00
Sandrine Duvet, Laurence Cocquerel, André Pillez, René Cacan, André Verbert, Darius Moradpour, Czeslaw Wychowski, Jean Dubuisson, Hepatitis C Virus Glycoprotein Complex Localization in the Endoplasmic Reticulum Involves a Determinant for Retention and Not Retrieval Journal of Biological Chemistry. ,vol. 273, pp. 32088- 32095 ,(1998) , 10.1074/JBC.273.48.32088
MinKyung Yi, Yinghong Ma, Jeremy Yates, Stanley M. Lemon, Compensatory Mutations in E1, p7, NS2, and NS3 Enhance Yields of Cell Culture-Infectious Intergenotypic Chimeric Hepatitis C Virus Journal of Virology. ,vol. 81, pp. 629- 638 ,(2007) , 10.1128/JVI.01890-06
Timothy L. Tellinghuisen, Katie L. Foss, Jason Treadaway, Regulation of hepatitis C virion production via phosphorylation of the NS5A protein. PLOS Pathogens. ,vol. 4, ,(2008) , 10.1371/JOURNAL.PPAT.1000032
Eike Steinmann, Francois Penin, Stephanie Kallis, Arvind H Patel, Ralf Bartenschlager, Thomas Pietschmann, Hepatitis C Virus p7 Protein Is Crucial for Assembly and Release of Infectious Virions PLOS Pathogens. ,vol. 3, ,(2007) , 10.1371/JOURNAL.PPAT.0030103
Frank Preugschat, Devron R. Averett, Berwyn E. Clarke, David J. T. Porter, A Steady-state and Pre-steady-state Kinetic Analysis of the NTPase Activity Associated with the Hepatitis C Virus NS3 Helicase Domain Journal of Biological Chemistry. ,vol. 271, pp. 24449- 24457 ,(1996) , 10.1074/JBC.271.40.24449
Takaji Wakita, Thomas Pietschmann, Takanobu Kato, Tomoko Date, Michiko Miyamoto, Zijiang Zhao, Krishna Murthy, Anja Habermann, Hans-Georg Kräusslich, Masashi Mizokami, Ralf Bartenschlager, T Jake Liang, Production of infectious hepatitis C virus in tissue culture from a cloned viral genome Nature Medicine. ,vol. 11, pp. 791- 796 ,(2005) , 10.1038/NM1268
Ardath K Yamaga, Jing-hsiung Ou, None, Membrane topology of the hepatitis C virus NS2 protein. Journal of Biological Chemistry. ,vol. 277, pp. 33228- 33234 ,(2002) , 10.1074/JBC.M202304200