Role of oxysterol binding protein in hepatitis C virus infection.
Hepatitis C virus (HCV) RNA genome replicates within the ribonucleoprotein (RNP) complex in the modified membranous structures extended from endoplasmic reticulum. A proteomic analysis of HCV RNP complexes revealed the association of oxysterol binding protein (OSBP) as one of the components of these complexes. OSBP interacted with the N-terminal domain I of the HCV NS5A protein and colocalized to the Golgi compartment with NS5A. An OSBP-specific short hairpin RNA that partially downregulated OSBP expression resulted in a decrease of the HCV particle release in culture supernatant with little effect on viral RNA replication. The pleckstrin homology (PH) domain located in the N-terminal region of OSBP targeted this protein to the Golgi apparatus. OSBP deletion mutation in the PH (DeltaPH) domain failed to localize to the Golgi apparatus and inhibited the HCV particle release. These studies suggest a possible functional role of OSBP in the HCV maturation process.
Amako
Yutaka
Y
Department of Medicine, University of California, San Diego, La Jolla, 92093, USA.
Sarkeshik
Ali
A
Hotta
Hak
H
Yates
John
J
Siddiqui
Aleem
A
D045744:Cell Line, Tumor; D006056:Golgi Apparatus / Q000378:metabolism; D016174:Hepacivirus / Q000502:physiology; D006526:Hepatitis C / Q000209:etiology*; D006801:Humans; D011485:Protein Binding; D021381:Protein Transport; D034741:RNA, Small Interfering / Q000494:pharmacology; D011987:Receptors, Steroid / Q000378:metabolism / Q000502:physiology*; D012261:Ribonucleoproteins; D017361:Viral Nonstructural Proteins / Q000378:metabolism*; D014764:Viral Proteins; D014779:Virus Replication; D000098825:Oxysterol Binding Proteins; D012324:RNA-Dependent RNA Polymerase
D034741:RNA, Small Interfering; D011987:Receptors, Steroid; D012261:Ribonucleoproteins; D017361:Viral Nonstructural Proteins; D014764:Viral Proteins; D000098825:Oxysterol Binding Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase