PMID- 29284752 OWN - NLM STAT- MEDLINE DCOM- 20180717 LR - 20181113 IS - 1091-6490 (Electronic) IS - 0027-8424 (Print) IS - 0027-8424 (Linking) VI - 115 IP - 2 DP - 2018 Jan 9 TI - Role of enhanced receptor engagement in the evolution of a pandemic acute hemorrhagic conjunctivitis virus. PG - 397-402 LID - 10.1073/pnas.1713284115 [doi] AB - Acute hemorrhagic conjunctivitis (AHC) is a painful, contagious eye disease, with millions of cases in the last decades. Coxsackievirus A24 (CV-A24) was not originally associated with human disease, but in 1970 a pathogenic "variant" (CV-A24v) emerged, which is now the main cause of AHC. Initially, this variant circulated only in Southeast Asia, but it later spread worldwide, accounting for numerous AHC outbreaks and two pandemics. While both CV-A24 variant and nonvariant strains still circulate in humans, only variant strains cause AHC for reasons that are yet unknown. Since receptors are important determinants of viral tropism, we set out to map the CV-A24 receptor repertoire and establish whether changes in receptor preference have led to the increased pathogenicity and rapid spread of CV-A24v. Here, we identify ICAM-1 as an essential receptor for both AHC-causing and non-AHC strains. We provide a high-resolution cryo-EM structure of a virus-ICAM-1 complex, which revealed critical ICAM-1-binding residues. These data could help identify a possible conserved mode of receptor engagement among ICAM-1-binding enteroviruses and rhinoviruses. Moreover, we identify a single capsid substitution that has been adopted by all pandemic CV-A24v strains and we reveal that this adaptation enhances the capacity of CV-A24v to bind sialic acid. Our data elucidate the CV-A24v receptor repertoire and point to a role of enhanced receptor engagement in the adaptation to the eye, possibly enabling pandemic spread. FAU - Baggen, Jim AU - Baggen J AD - Virology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, 3584CL Utrecht, The Netherlands. FAU - Hurdiss, Daniel L AU - Hurdiss DL AUID- ORCID: 0000-0003-3834-5808 AD - Astbury Centre for Structural Molecular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, United Kingdom. FAU - Zocher, Georg AU - Zocher G AD - Interfaculty Institute of Biochemistry, University of Tubingen, 72076 Tubingen, Germany. FAU - Mistry, Nitesh AU - Mistry N AD - Division of Virology, Department of Clinical Microbiology, Umea University, 90187 Umea, Sweden. FAU - Roberts, Richard W AU - Roberts RW AD - Virology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, 3584CL Utrecht, The Netherlands. FAU - Slager, Jasper J AU - Slager JJ AD - Virology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, 3584CL Utrecht, The Netherlands. FAU - Guo, Hongbo AU - Guo H AD - Virology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, 3584CL Utrecht, The Netherlands. FAU - van Vliet, Arno L W AU - van Vliet ALW AD - Virology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, 3584CL Utrecht, The Netherlands. FAU - Wahedi, Maryam AU - Wahedi M AD - Virology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, 3584CL Utrecht, The Netherlands. FAU - Benschop, Kimberley AU - Benschop K AD - Centre for Infectious Disease Control, National Institute for Public Health and the Environment, 3720BA Bilthoven, The Netherlands. FAU - Duizer, Erwin AU - Duizer E AD - Centre for Infectious Disease Control, National Institute for Public Health and the Environment, 3720BA Bilthoven, The Netherlands. FAU - de Haan, Cornelis A M AU - de Haan CAM AD - Virology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, 3584CL Utrecht, The Netherlands. FAU - de Vries, Erik AU - de Vries E AD - Virology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, 3584CL Utrecht, The Netherlands. FAU - Casasnovas, Jose M AU - Casasnovas JM AD - Department of Macromolecular Structures, Centro Nacional de Biotecnologia, Campus Universidad Autonoma de Madrid, 28049 Madrid, Spain. FAU - de Groot, Raoul J AU - de Groot RJ AD - Virology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, 3584CL Utrecht, The Netherlands. FAU - Arnberg, Niklas AU - Arnberg N AUID- ORCID: 0000-0002-7069-6678 AD - Division of Virology, Department of Clinical Microbiology, Umea University, 90187 Umea, Sweden. FAU - Stehle, Thilo AU - Stehle T AD - Interfaculty Institute of Biochemistry, University of Tubingen, 72076 Tubingen, Germany. FAU - Ranson, Neil A AU - Ranson NA AUID- ORCID: 0000-0002-3640-5275 AD - Astbury Centre for Structural Molecular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, United Kingdom. FAU - Thibaut, Hendrik Jan AU - Thibaut HJ AD - Virology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, 3584CL Utrecht, The Netherlands. FAU - van Kuppeveld, Frank J M AU - van Kuppeveld FJM AD - Virology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, 3584CL Utrecht, The Netherlands; F.J.M.vanKuppeveld@uu.nl. LA - eng SI - GENBANK/MG272373 SI - GENBANK/MG272374 SI - GENBANK/MG272375 SI - PDB/6EIT GR - Wellcome Trust/United Kingdom GR - 102572/B/13/Z/Wellcome Trust/United Kingdom GR - 108466/Z/15/Z/Wellcome Trust/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20171228 PL - United States TA - Proc Natl Acad Sci U S A JT - Proceedings of the National Academy of Sciences of the United States of America JID - 7505876 RN - 0 (Capsid Proteins) RN - 0 (Receptors, Virus) RN - 126547-89-5 (Intercellular Adhesion Molecule-1) RN - GZP2782OP0 (N-Acetylneuraminic Acid) SB - IM MH - Amino Acid Sequence MH - Capsid Proteins/genetics/metabolism MH - Conjunctivitis, Acute Hemorrhagic/epidemiology/*metabolism/virology MH - Cryoelectron Microscopy MH - Disease Outbreaks MH - Enterovirus C, Human/genetics/*metabolism/physiology MH - Humans MH - Intercellular Adhesion Molecule-1/chemistry/*metabolism MH - Mutation MH - N-Acetylneuraminic Acid/metabolism MH - Pandemics MH - Phylogeny MH - Protein Binding MH - Receptors, Virus/chemistry/*metabolism MH - Sequence Homology, Amino Acid MH - Viral Tropism/physiology PMC - PMC5777043 OTO - NOTNLM OT - ICAM-1 OT - conjunctivitis OT - coxsackievirus A24v OT - receptor OT - sialic acid COIS- The authors declare no conflict of interest. EDAT- 2017/12/30 06:00 MHDA- 2018/07/18 06:00 PMCR- 2018/07/09 CRDT- 2017/12/30 06:00 PHST- 2017/12/30 06:00 [pubmed] PHST- 2018/07/18 06:00 [medline] PHST- 2017/12/30 06:00 [entrez] PHST- 2018/07/09 00:00 [pmc-release] AID - 1713284115 [pii] AID - 201713284 [pii] AID - 10.1073/pnas.1713284115 [doi] PST - ppublish SO - Proc Natl Acad Sci U S A. 2018 Jan 9;115(2):397-402. doi: 10.1073/pnas.1713284115. Epub 2017 Dec 28.