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RESEARCH INTEREST

Publié le Monday 5 January 2009, by Webmaster

Research interests

The Hepatitis C Laboratory studies the interactions between hepatitis C virus (HCV) and the hepatocyte. This team has a long experience studying the biogenesis and functions of HCV envelope glycoproteins. The activity of the Hepatitis C Laboratory is also focused on the cell biology of the major steps of HCV life cycle.






HCV is a small enveloped positive-strand RNA virus that has been classified within the Hepacivirus genus, as part of the Flaviviridae family, which also comprises the general Flavivirus and Pestivirus. With approximately 170 million infected people, HCV is a major health problem worldwide. This virus often leads to chronic infection that can lead to chronic liver diseases, including cirrhosis and hepatocellular carcinoma. No vaccine is available to prevent new infections and only a fraction of patients treated with the currently available therapies respond to treatment. Basic research on this virus is therefore necessary for the development of new antiviral targets.

The recent developments of subgenomic replicons, retroviral particles pseudotyped with HCV envelope glycoproteins (HCVpp) and a cell culture system for HCV (HCVcc) provide all the necessary tools to study the major steps of HCV life cycle. Some related viruses like pestiviruses and flaviviruses are also used in some of our studies. A large part of our research activity is done in Lille. However, the group of Gilles Duverlie of the University of Amiens has recently been associated with the Hepatitis C Laboratory of Lille and some of the activities of the team are now also done at the University of Amiens.


Our current research activity is divided in four parts :


- Functional studies of HCV envelope glycoproteins,

- Cellular aspects of HCV entry,

- HCV replication and virus assembly

- Interactions between virus and host cell membranes in the Flaviviridae.


1/ Functional studies of HCV envelope glycoproteins

The Hepatitis C Laboratory has been pioneer in characterizing the biogenesis of HCV envelope glycoproteins. More recently, with the development of new tools to study HCV entry and infectivity, we have focused our research on functional studies of HCV envelope glycoproteins.




Comparison between the envelope proteins of HCV and the flaviviruses

Our objective is to identify functional domains in HCV envelope glycoproteins, characterize their role in virus entry and understand the role of N-linked glycosylation of HCV envelope glycoproteins. We are also interested by the signaling induced by HCV envelope glycoproteins when they interact with their receptor(s).



2/ Cellular aspects of HCV entry

Another aspect of our activity is to characterize cellular molecules involved in HCV entry. Several putative receptors have been identified for HCV and we concentrate our activity on two of them, the tetraspanin CD81 and the scavenger receptor BI. We are characterizing several partners of CD81 and their role in virus entry. We are also analyzing the role of some lipoproteins in HCV entry.

 

Finally, we are investigating the endocytic route used by HCV to penetrate into the hepatocyte.

 

3/ HCV replication and virus assembly

With the recent development of a cell culture system for HCV, we are now investigating some steps in virus assembly and replication. We are characterizing adaptive mutations that improve replication of the virus in tissue culture and we analyze interactions between viral proteins for the assembly of HCV particles. We are also interested by the role played by the innate immune response to control HCV replication.


4/ Interactions between virus and host cell membranes in the Flaviviridae

Interactions of viral proteins with host cell membranes is important for viruses to enter into host cells, replicate their genome and produce progeny particles. We are interested to characterize some steps of the life cycle of the Flaviviridae by analyzing the dynamics of virus-cell interactions by using model viruses of the Flaviviridae family. Our objective is to bring a dynamic dimension to the understanding of virus-cell interactions in the Flaviviridae family.