ArticleJournal of virology2013
Natural variation in the heparan sulfate binding domain of the eastern equine encephalitis virus E2 glycoprotein alters interactions with cell surfaces and virulence in mice.
Article in Journal of virology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 56 citations in OpenAlex.
- Spatial dynamics of viral replication drive biphasic lymphoid activation and systemic alphavirus immune responses.PLoS pathogens · 2026Article
- The residue 86 of the Getah virus E2 glycoprotein mediates both glycosaminoglycan- and LDLR-dependent infection.PLoS pathogens · 2026Article
- LRP4 is an entry receptor for multiple encephalitic alphaviruses.Nature communications · 2026Article
- Informed mutation of western equine encephalitis virus to heparan sulfate binding: Implications for rational design of alphavirus live attenuated vaccines.PLoS pathogens · 2026Article
- Glycosylation of GETV E2 promotes pathogenesis in animal models.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Discerning dangerous gain of function: most gain of function (GoF) research does not involve infectious microbes.Frontiers in bioengineering and biotechnology · 2026Review
- Three positively charged binding sites on the eastern equine encephalitis virus E2 glycoprotein coordinate heparan sulfate- and protein receptor-dependent infection.Nature communications · 2025Article
- Review
- Basic patches on the E2 glycoprotein of eastern equine encephalitis virus influence viral vascular clearance and dissemination in mice.Journal of virology · 2025Article
- A detailed kinetic model of Eastern equine encephalitis virus replication in a susceptible host cell.PLoS computational biology · 2025Article
- The VLDLR entry receptor is required for the pathogenesis of multiple encephalitic alphaviruses.Cell reports · 2024Article
- Phagocyte-expressed glycosaminoglycans promote capture of alphaviruses from the blood circulation in a host species-specific manner.PNAS nexus · 2024Article
- The low-density lipoprotein receptor promotes infection of multiple encephalitic alphaviruses.Nature communications · 2024Article
- Structural and functional basis of VLDLR receptor usage by Eastern equine encephalitis virus.bioRxiv : the preprint server for biology · 2023Article
- A molecular understanding of alphavirus entry and antibody protection.Nature reviews. Microbiology · 2023Review
- Article
- Is heparan sulfate a target for inhibition of RNA virus infection?American journal of physiology. Cell physiology · 2022Review
- Attenuation of Getah Virus by a Single Amino Acid Substitution at Residue 253 of the E2 Protein that Might Be Part of a New Heparan Sulfate Binding Site on Alphaviruses.Journal of virology · 2022Article
- Glycosaminoglycan binding by arboviruses: a cautionary tale.The Journal of general virology · 2022Review
- Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Recently, we compared amino acid sequences of the E2 glycoprotein of natural North American eastern equine encephalitis virus (NA-EEEV) isolates and demonstrated that naturally circulating viruses interact with heparan sulfate (HS) and that this interaction contributes to the extreme neurovirulence of EEEV (C. L. Gardner, G. D. Ebel, K. D. Ryman, and W. B. Klimstra, Proc. Natl. Acad. Sci. U. S. A., 108:16026-16031, 2011). In the current study, we have examined the contribution to HS binding of each of three lysine residues in the E2 71-to-77 region that comprise the primary HS binding site of wild-type (WT) NA-EEEV viruses. We also report that the original sequence comparison identified five virus isolates, each with one of three amino acid differences in the E2 71-to-77 region, including mutations in residues critical for HS binding by the WT virus. The natural variant viruses, which possessed either a mutation from lysine to glutamine at E2 71, a mutation from lysine to threonine at E2 71, or a mutation from threonine to lysine at E2 72, exhibited altered interactions with heparan sulfate and cell surfaces and altered virulence in a mouse model of EEEV disease. An electrostatic map of the EEEV E1/E2 heterotrimer based upon the recent Chikungunya virus crystal structure (J. E. Voss, M. C. Vaney, S. Duquerroy, C. Vonrhein, C. Girard-Blanc, E. Crublet, A. Thompson, G. Bricogne, and F. A. Rey, Nature, 468:709-712, 2010) showed the HS binding site to be at the apical surface of E2, with variants affecting the electrochemical nature of the binding site. Together, these results suggest that natural variation in the EEEV HS binding domain may arise during EEEV sylvatic cycles and that this variation may influence receptor interaction and the severity of EEEV disease.
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