F.-L. Cosset, PhD in molecular virology and vectorology in 1990 from University Claude Bernard Lyon-1, is currently the head of CIRI - International Center for Infectiology Research - Inserm U1111 - CNRS UMR5308 - at Ecole Normale Supérieure de Lyon - University Lyon-1. He is an expert in the molecular and cellular pathways that dictate assembly of viral surface glycoproteins on retroviral nucleocapsids, a process known as “pseudotyping”. His pioneering studies have led to the design of novel, shealthy human gene therapy vectors and to the development of new tools, allowing basic cell entry studies of pathogenic enveloped viruses, such as, e.g., HCV, which could not be grown in tissue culture in 2003. He thus reported the first HCV entry assay, so-called HCVpp (Bartosch et al. J. Exp. Med. 2003). This landmark discovery stimulated numerous studies from his own and many other groups towards in depth analysis of cell entry routes, identification of HCV receptors, mechanisms of neutralization and/or cell entry inhibition and humoral responses in patient cohorts. His team is composed of leading scientists in virology, viral engineering, vectorology, immunology, hematology and stem cell engineering, which provides tremendous expertise for biomedical applications. His work is supported by the European Union (ERC AdG HEPCENT).
The surface glycoproteins of enveloped viruses are structural components that are assembled on viral particles. They mediate interactions of virions with soluble host factors such as complement proteins or antibodies, for example, and govern entry into cells by interacting with different cellular factors. Our team is investigating the biology of surface glycoproteins derived from several different membrane-enveloped viruses, i.e., retroviruses, hepatitis C virus, influenza virus, paramyxovirus, etc… Ultimately, we aim to gain basic knowledge that should help us to: i) generate lentiviral vectors “pseudotyped”, i.e., coated with heterologous surface glycoproteins displaying specific properties in terms of cell surface interactions, ii) define immunogens that can elicit neutralizing antibodies against major pathogens such as influenza A virus and hepatitis C virus.
On the fundamental side, an important objective of a large part of our work is to understand the function and the regulation of these proteins at the level of i) the assembly of enveloped viral particles, ii) their interaction with the external environment, notably the innate and adaptive immune systems, and iii) the molecular processes governing the cellular entry of enveloped viruses and subsequent membrane fusion.
We are also pursuing studies aimed at optimizing methods allowing efficient gene delivery in vivo, by direct inoculation of defective viral vectors. The specific objectives are: i) the development of gene transfer vectors derived from onco-retroviruses and lentiviruses, ii) the investigation of strategies allowing a targeted gene transfer, restricted to cells expressing a specific cell surface receptor, through modifications of the viral surface glycoproteins. These studies will ultimately lead to the development of new tools suitable for in vivo transgenesis and human gene therapy.
Finally, our studies on viral engineering and more particularly on the viral surface glycoproteins allow several therapeutic applications, particularly in i) diagnostics, ii) antiviral compounds screening and iii) vaccine development. Some of these applications will be investigated, particularly in the field of hepatitis C and influenza.