
YAN LIU, Glycosciences Laboratory - Faculty of Medicine, Imperial College London
Seminar: Glycan microarrays for molecular dissection of virus-host interactions
Host: Angelina Palma, UCIBIO
Abstract
Glycan microarrays are important tools in elucidation of glycan receptors used by viruses to attach to host cells and initiate infections. The neoglycolipid (NGL)-based microarray system is an advanced glycan array platform that is available to the scientific community for recognition studies of diverse carbohydrate binding systems (http://www.imperial.ac.uk/glycosciences) [1]. The clustered and flexible presentation of non-covalently immobilized lipid-linked probes printed in a liposomal formulation on a nitrocellulose matrix renders the NGL system powerful in providing information on the molecular basis of the virus-host-glycan interactions including those of fastidious viruses [2]. There have been contributions to glycan recognition by a number of human pathogenic viruses, including the pandemic 2009 H1N1 influenza viruses isolated from infected humans [3].
I will focus on the recent contributions to collaborative studies with the groups of Thilo Stehle (Tübingen, Germany) and Niklas Arnberg (Umeå, Sweden) on recognition of host sialyl glycans by human viruses belonging to the Polyomaviridae and the Adenoviridae families. A highlight will be the discovery of polysialic acid sequences as high affinity ligands for the knob domain of the short fiber protein of human adenovirus 52 (HAdV-52), a gastroenteritis-associated virus. To our knowledge, this is the first time polysialic acid is identified as a cellular receptor for a human pathogenic virus [4]. Together with the data from protein structural and cellular biochemical studies, and knowledge of the overexpression of polysialic acid in brain and lung cancers, our findings amount to a novel mechanism for the human adenovirus entry into target cells, and there are implications for adenovirus-based cancer therapies.
References
1. Palma AS, Feizi T, Childs RA, Chai W, Liu Y. Curr Opin Chem Biol. 2014,18C, 87.
2. Childs RA, Palma AS, Wharton S, Matrosovich T, Liu Y, Chai W, Campanero-Rhodes MA, Zhang Y, Eickmann M, Kiso M, Hay A, Matrosovich M, Feizi T. Nat. Biotechnol. 2009, 27, 797.
3. Liu Y, Childs RA, Matrosovich T, Wharton S, Palma AS, Chai W, Daniels R, Gregory V, Uhlendorff J, Kiso M, Klenk HD, Hay A, Feizi T, Matrosovich M. J. Virol. 2010, 84, 12069.
4. Lenman A, Liaci AM, Liu Y, Frängsmyr L, Frank M, Blaum BS, Chai W, Podgorski II, Harrach B, Benkő M, Feizi T, Stehle T, Arnberg N. Proc Natl Acad Sci U S A, 2018, 11, E4264.
Short Bio
Dr Yan Liu completed her B.Sc. degree in chemistry at the Peking University in 2001, and obtained her PhD in organic chemistry from University of Bristol in 2005, under the guidance of Professor Tim Gallagher. She then joined the group of Professor Ten Feizi as one of the postdoc researchers funded by the UK Glycoarray Consortium and developed novel glycan probes for microarray studies. She was a named experienced investigator on the EPSRC Translational grant during 2008-2012 and her work has been extended to microarray analyses of diverse glycan-binding systems, notable among which are pandemic 2009 H1N1 influenza virus and other human pathogenic viruses of Papillomaviridae, Polyomaviridae and Adenoviridae families, Toxoplasma gondii and related apicomplexan parasites, and the broadly neutralizing anti-HIV antibodies. Since 2013, Dr Liu has been leading the Wellcome Trust-funded Carbohydrate Microarray Facility as a biomedical resource for the broad scientific community. Her expertise in the field of glycan arrays has been well recognized internationally. She is a member of the MIRAGE (Minimum Information Required for A Glycomics Experiment) Commission and the lead author of the recently published MIRAGE glycan microarray guidelines. Dr Liu is an accomplished chemist/glycobiologist with over 60 publications. Her main research interest is to develop ultrasensitive approaches to understand the roles of carbohydrate molecules in pathogen-host interactions and as potential biomarkers for infectious diseases and autoimmune diseases.