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Journal of Virology, September 2009, p. 9237-9246, Vol. 83, No. 18
0022-538X/09/$08.00+0     doi:10.1128/JVI.00958-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Role of Oxysterol Binding Protein in Hepatitis C Virus infection{triangledown} ,{dagger}

Yutaka Amako,1 Ali Sarkeshik,2 Hak Hotta,3 John Yates III,2 and Aleem Siddiqui1*

Department of Medicine, Division of Infectious Diseases, University of California, San Diego, La Jolla, California 92093,1 The Scripps Research Institute, Department of Chemical Physiology, 10550 North Torrey Pines Road, La Jolla, California 92037,2 Department of Microbiology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan3

Received 13 May 2009/ Accepted 19 June 2009

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 ({Delta}PH) 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.


* Corresponding author. Mailing address: Department of Medicine, Division of Infectious Diseases, Stein 409, University of California, San Diego, 9500 Gilman Dr., 0711, La Jolla, CA 92093. Phone: (858) 822-1750. Fax: (858) 822-1749. E-mail: asiddiqui{at}ucsd.edu

{triangledown} Published ahead of print on 1 July 2009.

{dagger} Supplemental material for this article may be found at http://jvi.asm.org/.


Journal of Virology, September 2009, p. 9237-9246, Vol. 83, No. 18
0022-538X/09/$08.00+0     doi:10.1128/JVI.00958-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.