Virus Entry and Regulation of Membrane Traffic
Project leader: Varpu Marjomäki, Ph.D.
Division of Cell and Molecular Biology, Nanoscience Center / Department of Biological and Environmental Science, University of Jyväskylä
P.O. Box 35, FIN-40014 University of Jyväskylä, Finland
Phone: +358 40 563 4422, Fax: +358 14 617 239, E-Mail email@example.com
Our work focuses on understanding the molecular mechanisms leading to successful infection by picornaviruses. In detail, we want to understand the factors regulating the membrane traffic from the plasma membrane to the endosomes that promote complex events such as virus uncoating, viral genome release and receptor down-regulation or recycling. Echovirus 1 (EV1) and its cellular receptor alpha2beta1 integrin are the key players that are following, but also coxsackieviruses A and B and other picornaviruses are studied. We have recently shown that EV1 clusters its receptor integrin and triggers their macropinocytic entry and accumulation in cytoplasmic neutral multivesicular bodies leading to integrin down-regulation and block in receptor recycling. In addition to defining the regulators of early entry, we are interested in understanding the ambient endosomal conditions leading to virus uncoating and genome release. Our previous studies have suggested interesting similarities between close relatives of echovirus such as coxsackie A 9.
Enteroviruses have recently been associated with chronic diseases such as type 1 diabetes, cardiomyopathies and atherosclerosis. In addition, enteroviruses have been identified among other virus groups as causative agents for gastroenteritis, which is a leading cause of infantile mortality worldwide. Despite their significance, there are no common drugs or vaccination against picornavirus infections other than for poliovirus. Fundamental cell biology studies are thus needed to understand the infectious entry pathways and to develop new antiviral strategies. Together with our collaborators we aim at the development and characterization of next generation vaccines strategies both in vitro and in vivo.
There is a great need for quantitative and reliable image acquisition. In order to fully extract the wealth of available information from a set of high quality images, we have recently developed an in-house BioImageXD software for quantitative light and electron microscope imaging together with our collaborators (www.bioimagexd.net; Kankaanpää et. al, 2012, Nature Methods).
Our studies are supported by Finnish Academy, TEKES FIDiPro program and JDRF (Juvenile Diabetes Research foundation).