Chronic Hepatitis C virus infections affect about 170 million people worldwide and constitute a significant risk factor for fibrosis, steatosis and hepatocellular carcinoma (HCC). HCV infections are a major indicator for liver transplantation. Here, we propose to characterize the role of lipids in virion morphogenesis mostly focusing on maturation and secretion from infected hepatocytes. In the previous grant we had identified and characterized the role of several lipids and lipid interacting proteins in affecting HCV secretion. Here, we propose to continue these studies and focus on the role of phosphatidylinosito-4 phosphate (PI4P)-interacting proteins including ceramide transfer protein (CERT), Nir-2, and Arfaptin in affecting the secretory transport of HCV virions across the Golgi network. HCV maturation/secretions through the Golgi network is believed to occur in association with very low-density lipoprotein (VLDL) assembly and secretion. VLDL transport occurs in specialized VLDL transport vesicles (VTVs). We propose to characterize the transport of HCV-associated VTVs across the Golgi network using an established biochemical fractionation procedure for isolating VTVs. Characterization of VTVs in HCV infected cells containing HCV virions components is of fundamental importance to the understating of HCV morphogenesis. We also propose to determine the functional importance of factors that affect VTVs in HCV maturation. These studies will reveal unique insight into the mechanisms of HCV maturation, secretion and egress and will serve as a model for other RNA viruses. The results of this study will open new avenues for therapeutic design of cellular targets affecting the HCV secretory pathway.

Public Health Relevance

Hepatitis C virus (HBV) infects about 3% of the world population and is a major indicator for liver transplantation. There is no vaccine available. HCV alters host lipid metabolic pathways for establishing infectious process. This proposal focuses on the role of lipids in the HCV maturation and secretion from infected hepatocytes.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
High Priority, Short Term Project Award (R56)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-IDM-U (02))
Program Officer
Koshy, Rajen
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of California San Diego
Internal Medicine/Medicine
Schools of Medicine
La Jolla
United States
Zip Code
Kim, Seong-Jun; Ahn, Dae-Gyun; Syed, Gulam H et al. (2018) The essential role of mitochondrial dynamics in antiviral immunity. Mitochondrion 41:21-27
Kim, Seong-Jun; Jang, Jae Young; Kim, Eun-Jung et al. (2017) Ginsenoside Rg3 restores hepatitis C virus-induced aberrant mitochondrial dynamics and inhibits virus propagation. Hepatology 66:758-771
Syed, Gulam H; Khan, Mohsin; Yang, Song et al. (2017) Hepatitis C Virus Lipoviroparticles Assemble in the Endoplasmic Reticulum (ER) and Bud off from the ER to the Golgi Compartment in COPII Vesicles. J Virol 91:
Khan, Mohsin; Syed, Gulam Hussain; Kim, Seong-Jun et al. (2015) Mitochondrial dynamics and viral infections: A close nexus. Biochim Biophys Acta 1853:2822-33
Till, Andreas; Saito, Rintaro; Merkurjev, Daria et al. (2015) Evolutionary trends and functional anatomy of the human expanded autophagy network. Autophagy 11:1652-67
Slagle, Betty L; Andrisani, Ourania M; Bouchard, Michael J et al. (2015) Technical standards for hepatitis B virus X protein (HBx) research. Hepatology 61:1416-24
Kim, Seong-Jun; Syed, Gulam H; Khan, Mohsin et al. (2014) Hepatitis C virus triggers mitochondrial fission and attenuates apoptosis to promote viral persistence. Proc Natl Acad Sci U S A 111:6413-8
Syed, Gulam Hussain; Tang, Huihui; Khan, Mohsin et al. (2014) Hepatitis C virus stimulates low-density lipoprotein receptor expression to facilitate viral propagation. J Virol 88:2519-29
Kim, Seong-Jun; Syed, Gulam H; Siddiqui, Aleem (2013) Hepatitis C virus induces the mitochondrial translocation of Parkin and subsequent mitophagy. PLoS Pathog 9:e1003285
Bishé, Bryan; Syed, Gulam H; Field, Seth J et al. (2012) Role of phosphatidylinositol 4-phosphate (PI4P) and its binding protein GOLPH3 in hepatitis C virus secretion. J Biol Chem 287:27637-47

Showing the most recent 10 out of 11 publications