Adenovirus: receptors, trafficking & vectorology

 Eric KREMER

 IGMM - UMR 5535

 1919, route de Mende, 34293 Montpellier

Phone: + 33 4 34 35 96 72

Email:eric.kremer@igmm.cnrs.fr

Website

The clarification of virus-cell interactions may be the most exciting aspect of modern virology, revealing similarities among virus families, the diversity of tropism, trafficking, and pathogen propagation. Our core theme is the study of adenoviruses, which normally cause subclinical symptoms, but in sporadic cases they can be lethal in infants and immune compromised patients. Our approaches transverse disciplines as diverse as virology, cellular and molecular biology, immunology, physical biochemistry, neurology, biochemistry, and gene transfer.

Fundamental research themes: We want to understand how adenoviruses interact with their primary and auxiliary cell surface receptors, how the internalised virus escapes endocytic vesicles, and once in the cytoplasm how it rapidly traffics along microtubules to the nucleus.

Applied research themes: We want to use the inherent properties of canine adenovirus (CAV-2), to generate gene transfer vectors that may be used to treat neurodegenerative disorders. Another basic tenet is to identify and overcome some of the potential clinical problems (e.g., memory and innate immunity) associated with adenovirus-mediated gene transfer.

Keywords: adenovirus, neurons, mucopolysaccharidosis, dendritic cells, virus receptors

Main publications

• Soudais C, Laplace-Builhe C, Kissa K & EJ Kremer. 2001 Preferential transduction of neurons by canine adenovirus vectors and their efficient retrograde transport in vivo. FASEB J Oct;15(12):2283-2285.
• Soudais C, Skander N & EJ Kremer. 2004 Long-term in vivo transduction of neurons throughout the rat CNS using novel helper-dependent CAV-2 vectors. FASEB J Feb;18(2):391-3.
• Hnasko TS, FA Perez, A Scouras, S Luquet, PE Phillips, EJ Kremer, RD Palmiter. 2006 Cre-mediated restoration of dopamine to the dorsal striatum of a dopamine-deficient mouse results in hyperphagia and hyperactivity. Proc Nat Acad Sci U S A. 2006 Jun 6;103(23):8858-63
• Perreau M, Pantaleo & EJ Kremer. 2008 Activation of a Dendritic Cell-T Cell Axis by Ad5 Immune Complexes Creates an Improved Environment for Replication of HIV in T Cells. J Experimental Medicine 205: 2717-2725
• Henaff D., E. Seiradake, H. Wodrich, O. Billet, M. Perreau, C. Hippert, F. Mennechet, G. Schoeh, H. Lortat-Jacob, H. Dreja, S. Ibanes, V. Kalatzis, J.P. Wang, R.W. Finberg, S. Cusack & EJ Kremer. 2009 The cell adhesion molecule CAR & sialic acid on human erythrocyte influence adenovirus biodistribution. PLoS Pathogens Jan;5(1):e1000277.
• Salinas S, Bilsland L, Henaff D, Weston AE, Keriel A, Schiavo G & EJ Kremer. 2009. CAR-associated vesicular transport of an adenovirus in motor neuron axons. PLoS Pathogens May;5(5):e1000442.
• Wodrich H, Henaff D, Jammart B, Segura-Morales C, Seelmeier S, Coux O, Ruzsics Z, Wiethoff C & EJ Kremer. 2010 A capsid encoded PPxY motif facilitates adenovirus entry. PLoS Pathogens Mar 19;6(3):e1000808.
• Bennasser Y, C Chable-Bessia, R Triboulet, D Gibbings, C Gwizdek, C Dargemont, EJ Kremer, O Voinnet & M. Benkirane. 2011 Competition for XPO5 binding between Dicer mRNA, pre-miRNA and viral RNA regulates human Dicer levels. Nature Structure & Molecular Biology Mar;18(3):323-7
• Kremer EJ, 2009 Mutagenesis of hexon "FX" hepatic tropism. Blood 114(5):929-30
• Salinas S, Schiavo G & EJ Kremer. 2010. A hitchhiker's guide to the nervous system: the complex journey of viruses and toxins. Nature Reviews Microbiology Sep;8(9):645-55