Formation and function of hepatitis C virus replication complexes require residues in the carboxy-terminal domain of NS4B protein
Abstract During replication, hepatitis C virus (HCV) NS4B protein rearranges intracellular membranes to form foci, or the web, the putative site for HCV replication. To understand the role of the C-terminal domain (CTD) in NS4B function, mutations were introduced into NS4B alone or in the context of...
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| Veröffentlicht in: | Virology (New York, N.Y.) N.Y.), 2009-10, Vol.393 (1), p.68-83 |
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| creator | Aligo, Jason Jia, Shuaizheng Manna, David Konan, Kouacou V |
| description | Abstract During replication, hepatitis C virus (HCV) NS4B protein rearranges intracellular membranes to form foci, or the web, the putative site for HCV replication. To understand the role of the C-terminal domain (CTD) in NS4B function, mutations were introduced into NS4B alone or in the context of HCV polyprotein. First, we show that the CTD is required for NS4B-induced web structure, but it is not sufficient to form the web nor is it required for NS4B membrane association. Interestingly, all the mutations introduced into the CTD impeded HCV genome replication, but only two resulted in a disruption of NS4B foci. Further, we found that NS4B interacts with NS3 and NS5A, and that mutations causing NS4B mislocalization have a similar effect on these proteins. Finally, we show that the redistribution of Rab5 to NS4B foci requires an intact CTD, suggesting that Rab5 facilitates NS4B foci formation through interaction with the CTD. |
| doi_str_mv | 10.1016/j.virol.2009.07.033 |
| format | Article |
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To understand the role of the C-terminal domain (CTD) in NS4B function, mutations were introduced into NS4B alone or in the context of HCV polyprotein. First, we show that the CTD is required for NS4B-induced web structure, but it is not sufficient to form the web nor is it required for NS4B membrane association. Interestingly, all the mutations introduced into the CTD impeded HCV genome replication, but only two resulted in a disruption of NS4B foci. Further, we found that NS4B interacts with NS3 and NS5A, and that mutations causing NS4B mislocalization have a similar effect on these proteins. Finally, we show that the redistribution of Rab5 to NS4B foci requires an intact CTD, suggesting that Rab5 facilitates NS4B foci formation through interaction with the CTD.</description><identifier>ISSN: 0042-6822</identifier><identifier>EISSN: 1096-0341</identifier><identifier>DOI: 10.1016/j.virol.2009.07.033</identifier><identifier>PMID: 19703698</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Amino Acid Sequence ; Cell Membrane - metabolism ; Cell Membrane - ultrastructure ; Cell Membrane - virology ; DNA Mutational Analysis ; HCV ; Hepacivirus - genetics ; Hepacivirus - physiology ; Hepacivirus - ultrastructure ; Hepatitis C virus ; Host-Pathogen Interactions ; Infectious Disease ; Membrane-association ; Membranous web ; Microscopy, Confocal ; Microscopy, Electron, Transmission ; Molecular Sequence Data ; Mutant Proteins - genetics ; Mutant Proteins - physiology ; NS3 ; NS4B ; NS5A ; Protein Binding ; Protein Interaction Domains and Motifs ; rab5 GTP-Binding Proteins - metabolism ; Replication complex ; Sequence Alignment ; Subcellular localization ; Viral Nonstructural Proteins - genetics ; Viral Nonstructural Proteins - metabolism ; Viral Nonstructural Proteins - physiology ; Virus Replication</subject><ispartof>Virology (New York, N.Y.), 2009-10, Vol.393 (1), p.68-83</ispartof><rights>Elsevier Inc.</rights><rights>2009 Elsevier Inc.</rights><rights>2009 Elsevier Inc. 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To understand the role of the C-terminal domain (CTD) in NS4B function, mutations were introduced into NS4B alone or in the context of HCV polyprotein. First, we show that the CTD is required for NS4B-induced web structure, but it is not sufficient to form the web nor is it required for NS4B membrane association. Interestingly, all the mutations introduced into the CTD impeded HCV genome replication, but only two resulted in a disruption of NS4B foci. Further, we found that NS4B interacts with NS3 and NS5A, and that mutations causing NS4B mislocalization have a similar effect on these proteins. 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| source | MEDLINE; Elsevier ScienceDirect Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Amino Acid Sequence Cell Membrane - metabolism Cell Membrane - ultrastructure Cell Membrane - virology DNA Mutational Analysis HCV Hepacivirus - genetics Hepacivirus - physiology Hepacivirus - ultrastructure Hepatitis C virus Host-Pathogen Interactions Infectious Disease Membrane-association Membranous web Microscopy, Confocal Microscopy, Electron, Transmission Molecular Sequence Data Mutant Proteins - genetics Mutant Proteins - physiology NS3 NS4B NS5A Protein Binding Protein Interaction Domains and Motifs rab5 GTP-Binding Proteins - metabolism Replication complex Sequence Alignment Subcellular localization Viral Nonstructural Proteins - genetics Viral Nonstructural Proteins - metabolism Viral Nonstructural Proteins - physiology Virus Replication |
| title | Formation and function of hepatitis C virus replication complexes require residues in the carboxy-terminal domain of NS4B protein |
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