“The development of therapeutics has been difficult because so far it has been impossible to produce HCV particles in vitro.”

This paper describes for the first time an infection assay for hepatitis C virus (HCV) which can be handled in a reproducible and accurate manner in conventional laboratories. Since the discovery of HCV 14 years ago no laboratory has succeeded in establishing reliable surrogate HCV infection models that enable the study of HCV glycoproteins, their structure, their assembly, their cell surface receptors, and their roles in cell entry, as well as the humoral immune response against HCV. As published in our follow-up papers, this is now rendered possible using this new assay, which was judged to constitute a milestone in HCV research with an impact similar to that of HCV replicons. The functionality and infectivity of HCVpp has now been confirmed by others and we have had extensive interest in the system from a significant number of academic and private laboratories all over the world.

  Could you summarize the significance of your paper in layman's terms?

World-wide several hundred million people, or in other words about 3% of the world population, are infected with HCV. Progression to chronic disease occurs in the majority of HCV-infected persons. Infection is associated with an increased risk for liver diseases and hepatocellular carcinoma, and has become the main indication for liver transplantation. No vaccine is currently available to prevent new infections and treatment possibilities are still limited. Clearly, novel therapeutic strategies are urgently required as the health costs for HCV-infected people are predicted to spiral dramatically in the next few decades. The development of therapeutics has been difficult because so far it has been impossible to produce HCV particles in vitro. Thus the availability of our infection assay opens different avenues to develop therapeutics, such as the screening of anti-viral inhibitors and the development of vaccines, in addition to its importance for fundamental research.

My laboratory has been investigating the functions and properties of surface glycoproteins from several enveloped viruses for several years. The envelope glycoproteins are involved in many steps of the viral life cycle, such as virion assembly, interaction with the innate and adaptive host immune system, recognition of the target cells and viral tropism, cell attachment, membrane fusion, and cell entry routes. Our studies aim to find a molecular description of these different steps. We believe that understanding the properties of these essential viral components in the cell entry and membrane fusion processes will contribute significantly to our understanding of the basic biology of viral infection and its pathogenesis, and that it will also initiate the development of novel therapeutic strategies in both clinical and diagnostic as well as in other medical research areas. A second area of research in my laboratory is related to the design and evaluation of gene transfer vectors derived from retroviruses and lentiviruses. Our recent research has also allowed us to overcome several barriers to gene delivery in vivo. We therefore gained considerable valuable experience in the engineering of viral vectors, particularly in the formation of retroviral pseudotypes—which consist of retroviral core particles enveloped with heterologous glycoproteins.

Thus the HCV pseudo-particle project was a logical extension of this background and offered the opportunity to study a novel class of envelope glycoproteins as well as to contribute to the development of tools for HCV therapy.