Abstract

Hepatitis C virus infections most often lead to chronic hepatitis, which can progress to liver cirrhosis and hepatocellular carcinoma. The infection is also associated with steatosis. HCV alters lipid homeostasis. HCV stimulates lipogenesis, impairs mitochondrial -oxidation and lipid export. These altered lipid metabolic activities benefi viral infectious process. Several lipid molecules affect viral replication, assembly, maturation and secretion. In this resubmission of our application, we continue to investigate molecular mechanism(s) associated with HCV-induced alteration of host lipid metabolism. Our current focus will be on effect of HCV gene expression on mitochondrial -oxidation and the mitochondrial dysfunctions associated with chronic hepatitis C. We propose to investigate the effects of HCV gene expression on mitochondrial enzymes involved in lipid metabolism, and mechanisms of clearance of damaged mitochondria via mitophagy. These studies provide a unique insight and open avenues of investigations into HCV-associated liver disease pathogenesis

Public Health Relevance

Hepatitis C virus (HCV) infects about 2-3% of world population. HCV infection is a major risk for the development of hepatocellular carcinoma (HCC) and an indicator for liver transplant. This proposal aims to examine the role of HCV on mitochondrial metabolism, physiology and dynamics and its contribution to liver disease pathogenesis.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK077704-07
Application #
8792381
Study Section
Hepatobiliary Pathophysiology Study Section (HBPP)
Program Officer
Doo, Edward
Project Start
2007-04-01
Project End
2017-12-31
Budget Start
2015-01-01
Budget End
2015-12-31
Support Year
7
Fiscal Year
2015
Total Cost
$337,125
Indirect Cost
$119,625

  Institution

Name
University of California San Diego
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093

  Publications

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
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; 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
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 15 publications