Interaction of hepatitis C virus F protein with prefoldin 2 perturbs tubulin cytoskeleton organization.
By use of the yeast two-hybrid system, hepatitis C virus (HCV) F protein was found to interact with a cellular protein named prefoldin 2. The interaction was confirmed by confocal immunofluorescence microscopy as well as coimmunoprecipitation experiments. Prefoldin 2 is a subunit of a hexameric molecular chaperone complex, named prefoldin, which delivers nascent actin and tubulin proteins to the eukaryotic cytosolic chaperonin for facilitated folding. Functional prefoldin spontaneously assembles from its six subunits (prefoldin 1-6). In the yeast three-hybrid system, it was found that expression of HCV F protein impeded the interaction between prefoldin 1 and 2. By performing immunofluorescence experiment and non-denaturing gel electrophoresis, it was shown that expression of HCV F protein resulted in aberrant organization of tubulin cytoskeleton. Since HCV replication requires intact microtubule and actin polymerization, HCV F protein may serve as a modulator to prevent high level of HCV replication and thus contributes to viral persistence in chronic HCV infection.
Tsao
Mei-Ling
ML
Liver Research Unit, Chang Gung Memorial Hospital, Taipei, Taiwan.
Chao
Chung-Hao
CH
Yeh
Chau-Ting
CT
D000818:Animals; D002522:Chlorocebus aethiops; D003599:Cytoskeleton / Q000378:metabolism / Q000648:ultrastructure; D015967:Gene Expression Regulation, Viral; D016174:Hepacivirus / Q000502:physiology; D019698:Hepatitis C, Chronic / Q000378:metabolism / Q000821:virology; D006801:Humans; D018832:Molecular Chaperones / Q000378:metabolism*; D011485:Protein Binding; D014404:Tubulin / Q000378:metabolism; D014709:Vero Cells; D014758:Viral Core Proteins / Q000378:metabolism*; D014779:Virus Replication
D018832:Molecular Chaperones; D014404:Tubulin; D014758:Viral Core Proteins; C433031:hepatitis C protein F, Hepatitis C virus; C112806:prefoldin