CV Science

Patrice André MD, PhD, Professor Virology, Medical Virology and Cell biology of Viral Infection

Course and current status

Degrees

Medical Doctor, Brest, 1982.

PhD, Université de Rennes, Sciences de la Vie, 1988.

Habilitation à diriger les recherches, 1993.

Certificat de Bactériologie Systématique : Institut Pasteur, Paris, 1981.

Certificat de Virologie Systématique : Institut Pasteur, Paris, 1981.

Certificat d'Immunologie Générale : Institut Pasteur, Paris, 1982.

Certificat d'Immunologie Microbienne : Institut Pasteur, Paris, 1982.

"Educational Commission for Foreign Medical Graduates", U.S.A., 1985.

Certificat de Virologie Générale : Institut Pasteur, Paris, 1987.

Previous Positions       

1977-1978 Military medical service in Morocco. 

1976-1981 Resident in Medicine, Brest University Hospital.

1982 Grant recipient "Recherche Clinique" Institut G. Roussy, Villejuif.

1983-1985 "Post doctoral fellow" Cell Biology Department, Univ. New Mexico.1985-1990 Assistant des hôpitaux, Assistant des universités, Medical School, University Rennes1 and Rennes University Hospital.

1990-1999 Associate Professor – Praticien hospitalier, Medical School, University Rennes1 and Rennes University Hospital.

1999-2003 Associate Professor -Praticien hospitalier, Lyon Nord Medical School, University Lyon1, and Hospices Civils de Lyon.

Fonctions, Current Positions                       

First class Professor of Virology, Charles Mérieux- Lyon Sud Medical School, University Claude Bernard Lyon 1.

Head of virology laboratory, Hôpital de la Croix-Rousse, Hospices Civils de Lyon.

Research Team Leader, CIRI, INSERM Unit U1111.

Scientific summary

This research team "Cell biology of viral infection" at the International center of Research in Infectiology, Inserm U1111-CNRS UMR5308, Lyon University, directed by V. Lotteau and P. André is dedicated to the cell biology of viral infections. The identification of cellular functions that are used by viruses to replicate constitutes the core expertise of this group. The team is studying viral mechanisms involved in the changes of cellular functions regulating viral replication. In the infectious disease center of Lyonbiopôle, this team has created a systems biology platform for the rational identification of therapeutic targets and drug discovery.

In a systems biology approach, viral pathogenesis can be considered as the expression of new constraints generated by the viral proteins on the network of cellular proteins interactions constituting its interactome. The team sought to determine by high-throughput screening the interactions between the proteomes of several viruses and cellular proteins and these data have been collected in various databases (ViralORFeome - VirHostNet - pistil). Determining the interactions between viral proteins and cellular proteins has allowed the reconstruction of subnetworks strongly impacted by the virus, such as that of the type I interferon, TGF-b or metabolism.

With its unique database integrating interactomics and functional genomics and its knowledge on how viruses perturb cell host functions, the platform can identify relevant targets for the development of host-oriented molecules. Network pharmacology allows selection of therapeutic molecules, using a drug repurposing strategy and an original library of interfering peptides targeting cellular generic processes. The platform now offers tools to manipulate a large panel of original therapeutic targets for infectious and non-communicable chronic diseases. Internal lead programs first concerned influenza A, hepatitis B and hepatitis C viruses for which targets and molecules have been patented. Second wave programs are concerning HIV and viruses of medical interest as well as Insulin resistance and mitochondrion dysfunction. In addition, the platform has developed an innovative method for reading transcriptomic data from pathway reconstruction to drug discovery.

The relationship between viral infection and host metabolism is particularly studied by the team through models of viral hepatitis B and C. Both viruses exemplify how viruses can benefit from their interaction with the bio-energetic metabolism of the cell. The hepatitis C virus directly impacts the bio-energetic and central carbon metabolism of hepatocytes with obvious implications clinically and biologically at the host level. Indeed chronic hepatitis C infection leads to a particular metabolic syndrome associating insulin resistance, fatty liver and hypobetalipoproteinemia. HCV replication is closely dependent, at all stages of the replication cycle, to lipid metabolism, including synthesis of VLDL. Our team has shown that highly infectious HCV particles that circulate in patients are hybrid lipo-viral particles (LVP), which are betalipoproteins, VLDL and LDL, modified by the presence of a nucleocapsid in the lipid core and of viral envelope proteins at the surface of these particles. It was thus shown for the first time that the virus could interfere with lipoprotein assembly to achieve hybrid particles and this discovery has opened up new perspectives. The team is particularly interested in the identification of signals carried by these particles to the adjacent liver tissue or to peripheral tissues to understand the pathogenesis of insulin resistance that characterizes this viral hepatitis. Although the hepatitis B virus induces only low metabolic disturbances in the liver of the host, it was labeled as a "métabolovirus" because its replication is closely dependent on metabolic signals received by hepatocytes through nuclear receptors and epigenetic regulation of viral gene transcription. The team has shown in particular that the bile salt nuclear receptor FXR is a crucial factor in the control of viral replication and continues to study the role of fasting and satiety signals, as well as the energy status of the cell on HBV replication.