Symmetry-Related Clustering of Positive Charges Is a Common Mechanism for Heparan Sulfate Binding in Enteroviruses
- 15 October 2012
- journal article
- Published by American Society for Microbiology in Journal of Virology
- Vol. 86 (20), 11163-11170
- https://doi.org/10.1128/jvi.00640-12
Abstract
Coxsackievirus A9 (CAV9), a member of the Picornaviridae family, uses an RGD motif in the VP1 capsid protein to bind to integrin αvβ6 during cell entry. Here we report that two CAV9 isolates can bind to the heparan sulfate/heparin class of proteoglycans (HSPG). Sequence analysis identified an arginine (R) at position 132 in VP1 in these two isolates, rather than a threonine (T) as seen in the nonbinding strains tested. We introduced a T132R substitution into the HSPG-nonbinding strain Griggs and recovered infectious virus capable of binding to immobilized heparin, unlike the parental Griggs strain. The known CAV9 structure was used to identify the location of VP1 position 132, 5 copies of which were found to cluster around the 5-fold axis of symmetry, presumably producing a region of positive charge which can interact with the negatively charged HSPG. Analysis of several enteroviruses of the same species as CAV9, Human enterovirus B (HEV-B), identified examples from 5 types in which blocking of infection by heparin was coincident with an arginine (or another basic amino acid, lysine) at a position corresponding to 132 in VP1 in CAV9. Together, these data show that membrane-associated HSPG can serve as a (co)receptor for some CAV9 and other HEV-B strains and identify symmetry-related clustering of positive charges as one mechanism by which HSPG binding can be achieved. This is a potentially powerful mechanism by which a single amino acid change could generate novel receptor binding capabilities, underscoring the plasticity of host-cell interactions in enteroviruses.Keywords
This publication has 45 references indexed in Scilit:
- Structural Basis of Oligosaccharide Receptor Recognition by Human PapillomavirusOnline Journal of Public Health Informatics, 2011
- Interaction of α V β 3 and α V β 6 Integrins with Human Parechovirus 1Journal of Virology, 2010
- Internalization of Coxsackievirus A9 Is Mediated by β2-Microglobulin, Dynamin, and Arf6 but Not by Caveolin-1 or ClathrinJournal of Virology, 2010
- A Dominant-Negative Mutant of rab5 Inhibits Infection of Cells by Foot-and-Mouth Disease Virus: Implications for Virus EntryJournal of Virology, 2009
- Role of Cellular Heparan Sulfate Proteoglycans in Infection of Human Adenovirus Serotype 3 and 35PLoS Pathogens, 2008
- Human Rhinovirus Type 54 Infection via Heparan Sulfate Is Less Efficient and Strictly Dependent on Low Endosomal pHJournal of Virology, 2007
- Primary attachment of murine leukaemia virus vector mediated by particle-associated heparan sulfate proteoglycanBiochemical Journal, 2006
- N- and 6-O-Sulfated Heparan Sulfates Mediate Internalization of Coxsackievirus B3 Variant PD into CHO-K1 CellsJournal of Virology, 2006
- Mutations in the E2 Glycoprotein of Venezuelan Equine Encephalitis Virus Confer Heparan Sulfate Interaction, Low Morbidity, and Rapid Clearance from Blood of MiceVirology, 2000
- CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choiceNucleic Acids Research, 1994