Flavivirus-Host Molecular Interactions  


  HEADDr. Philippe DESPRES / pdespres@pasteur.fr
  MEMBERSDr. Matthieu BLANCHET / Jean-Baptiste BRAULT / Anne-Claire BREHIN / Dr. Lark COFFEY / Marie-Pascale FRENKIEL/ Petra GEST / Eva MERTENS / Brigitte MILLIOT / Dr. Nathalie PARDIGON


  Annual Report

The laboratory Flavivirus-Host Molecular Interactions is dedicated to the understanding of molecular interactions between viral and host factors that contribute to the pathogenicity of emerging arboviruses such as flaviviruses dengue (DEN) and West Nile (WN), and alpahvirus Chikungunya (CHIK). The knowledge of such mechanisms has important implications for medical vaccine design and will yield crucial informations to guide diagnostic development and therapeutic strategies against arboviroses of global interest in public health.

Emerging arboviroses are defined as arthropod-borne viral diseases that have newly appeared in a population or existed already but are rapidly increasing in incidence or geographic range. The resurgence of DEN and CHIK in tropical and subtropical areas of the world and establishment of WN in Western Hemisphere illustrate the propensity of mosquito-borne RNA viruses to spread and colonize new areas.

Cellular partners that interact with flavivirus proteins. The yeast two-hybrid technology allowed the identification of a human cellular protein which interact with most of flavivirus membrane M proteins.Studies are undertaken to understand the role of an identified cellular interactor to M in the pathogenicity of flaviviruses. We have now extended our study by analyzing the cellular interactors to non-structural proteins from neurotropic flaviviruses.

(in collaboration with P.O. Vidalain).

In vivo and in vitro studies of pathogenic properties of CHIK virus strains from La Réunion. For these studies, we have generated a library of mouse monoclonal antibodies reactive to CHIK envelope E2 glycoprotein. We have identified viral genetic elements that contribute to the pathogenicity of CHIK virus in mosquito vector and mammalian hosts.

(in collaboration with A-B. Failloux et M. Lecuit)

Interferon (IFN)-mediated antiviral pathways playing a role in the innate immunity to arboviruses. We reported that IFN-inducible 2’-5’ Oligo-Adenylate Synthetase (OAS) genes function as antiviral molecules against flaviviruses. We have characterized viral genetic elements that may account for the resistance of flavivirus to antiviral action of OAS. We are pursuing the identification of OAS genes and their genetic variants which are involved in the severity of arbovirus infection in humans.

(in collaboration with A. Sakuntabhai and J.J. Panthier).

An affordable dengue vaccine that can be used in young populations living in tropical countries. The candidate dengue vaccine is based on the expression of a combined dengue antigen by a live-attenuated vector derived from pediatric Schwarz measles vaccine.

(in collaboration with F. Tangy).

Keywords: arbovirus, flavivirus, alphavirus, dengue, West Nile, Chikungunya, viral pathogenicity, innate immunity, vaccine

Imfh.jpg

Electron microscopy of Dengue virus (courtesy MC Prevost)



  Publications

Bréhin, A.C., Rubrecht, L., Navarro-Sanchez, M.E., Maréchal, V., Frenkiel M-P., Lapalud P. , Laune, D., Sall, A.A, and Desprès, P. (2008). Production and characterization of mouse monoclonal antibodies reactive to Chikungunya envelope E2 glycoprotein. Virology, 371 :185-195

Brandler, S., Lucas-Hourani, M., Moris, A., Frenkiel, M-P., Combredet, C., Février, C., Bedouelle, H., Schwartz, O., Desprès, P., and Tangy, F. (2007). Pediatric measles vaccines expressing a dengue antigen induces durable serotype-specific neutralizing antibodies to dengue virus. PloS Negl Trop Dis 1(3):e96.

Kajaste-Rudnitski, A., Mashimo, T., Frenkiel, M-P., Guénet, J.-L., Lucas, M., and Desprès, P. (2006). The 2’-5’-Oligoadenylate Synthetase 1b is a potent inhibitor of West Nile replication inside infected cells. J.Biol. Chem.281 : 4624-37.

Desprès, P. , Combredet, C., Frenkiel, M-P., Lorin, C., Brahic, M. and Tangy, F. (2005). Live measles vaccine expressing the secreted form of the West Nile virus envelope glycoprotein protects against West Nile virus encephalitis. J.Infect.Dis. 191 : 207-14.

Sakuntabhai, A., Turbpaiboo, C., Casadémont, I., Lowhnoo, A., Chuansumrit, T., Kajaste-Rudnitski, A., [12 co-authors], Lathrop, M., Malasit, P., Desprès, P., and Julier, C. (2005). A variant in the CD209 (DC-SIGN) promoter is associated with the severity of dengue disease. Nat. Genet.37:507-13





Activity Reports 2007 - Institut Pasteur
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