Host factor interactions during early steps of Hepatitis C Virus cell entry and their inter-individual modulation by genetic and pharmacological perturbations
The hepatitis C virus causes a chronic infection of the liver, which in the long run can lead to scarring of the liver (liver cirrhosis), liver failure and liver cancer. Approximately 71 million people worldwide are chronically infected with hepatitis C. The disease is known to cause liver cancer. Although hepatitis C is curable today, many people, especially in underprivileged countries, are unaware of their infection and have no access to treatment. Unfortunately, a preventive vaccine is not yet available.
Clinically it has been shown that there are individual differences in the course of hepatitis C infection. An estimated 70 to 75% of those exposed develop a chronic infection. Of these, about 30% must expect the development of liver damage after 15 to 20 years without therapeutic intervention. Why people react differently to a hepatitis C infection is currently poorly understood.
The research groups led by Gisa Gerold and Thomas von Hahn are investigating how inter-individual differences influence hepatitis C infection. Their main focus is on genetic variations in humans and treatment with lipid-reducing drugs. The latter is based on the fact that the virus interacts strongly with the human lipid metabolism. The researchers look at how the virus penetrates liver cells and then multiplies. When entering liver cells, the virus uses several human proteins that form a complex on liver cells and play a central role in human fat metabolism. Gisa Gerold’s and Thomas von Hahn’s teams are investigating how this complex, i.e. the entry portal of the virus, is altered by genetic variants and pharmacological intervention in the lipid metabolism, which ultimately influences virus proliferation and the progression of chronic hepatitis C. They hope to gain new insights into the function of the hepatitis C virus, new diagnostic possibilities and, in the long term, new therapeutic approaches.
The HCV replication cycle and the clinical course of hepatitis C are modulated by genetic and non-genetic variation in the host. CD81, CAPN5, CBLB and SR-BI – the latter a physiological hepatic receptor for lipoproteins – are important host factors for HCV and essential for cell entry of the virus. Numerous genetic variants exist in the genes encoding these five factors. Many of them have a clinical phenotype, mostly in the form of an altered serum lipid profile. However, the effects of these variants on chronic HCV infection are unknown. Moreover, the extent to which drugs that influence lipid metabolism modulate HCV infection remains enigmatic. This project aims to clarify how variation in HCV entry factors and non-genetic factors, such as lipid-reducing drugs, affect the HCV replication cycle and the ability of the virus to establish and maintain a chronic infection.
The project has four parts:
Gisa Gerold is talking about her research at CRC 900
Gisa Gerold jointed the project at the start of the third funding period in 2018. Together with Thomas von Hahn she is jointly leading the project C7, which addresses the influence of different gene variants and the pharmacological intervention in lipid metabolism on the course of infection with hepatitis C virus.
Thomas von Hahn is talking about his research at CRC 900
Thomas von Hahn joined the CRC at the start of the second funding period in 2014. Together with Gisa Gerold he is jointly leading the project C7, which addresses how various variants of a gene with a central role in fat metabolism influence the course of infection with hepatitis C virus.
Publications of the project C7
Prof. Dr. Gisa Gerold
Department of Biochemistry
Research Center for Emerging Infections and Zoonosis (RIZ)
University of Veterinary Medicine Hannover
+49 511 953 6146
Prof. Thomas von Hahn
Department of Gastroenterology, Hepatology und Endocrinology
Hannover Medical School
+49 511 532-2406