Impact of host variation in the Sec14L2 gene on the development and maintenance of chronic hepatitis C
The hepatitis C virus (HCV), a leading cause of cirrhosis and liver cancer, utilizes a number of host encoded cofactors to infect and replicate in human hepatocytes. Among these, the protein Sec14L2 stands out because it enables pan-genotype HCV replication in cell culture . The replication cycle of the hepatitis C virus (HCV) and the clinical course of hepatitis C are modulated by genetic and non-genetic variation of the host. Numerous genetic variants exist in the Sec14L2 gene. One of these variants has a clinical phenotype, mostly in the form of an altered cancer frequency. However, their effect on chronic HCV infection is unknown. This project has two parts: (1) all known coding non-synonymous Sec14L2 variants will be tested for their effect on the HCV replication cycle in in vitro; (2) all known Sec14L2 variants, coding or non-coding, with a minor allele frequency of at least 5% will be tested for their effect on the development, progression and treatment response of chronic HCV infection in cohorts of acutely and chronically HCV infected individuals.
Methods that will be used:
Key approaches of this project will include cell culture, molecular biology techniques, the biochemical and microscopy-based quantification of protein function. Most aspects of this study will include work with infectious HCV at the security level 3.
National and international partners
Profile of candidate’s qualification:
The successful candidate should have a strong background and interest in virology, good organization skills, and a very high level of motivation to conduct creative and independent research.
Source of Funding: University Hospital Essen
Stoehr, S et al: Host cell mTORC1 is required for HCV RNA replication. Gut 2015
Deest M et al.:Impact of single nucleotide polymorphisms in the essential HCV entry factor CD81 on HCV infectivity and neutralization. Antiviral Research 2014
von Hahn et al.: Hepatocytes that express variants of cyclophilin A are resistant to HCV infection and replication. Gastroenterology 2012