ArticleJournal of virology2007
Heparan sulfate binding can contribute to the neurovirulence of neuroadapted and nonneuroadapted Sindbis viruses.
Article in Journal of virology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed, 82 citations in OpenAlex.
- The pathogenicity and virulence of Sindbis virus.Virulence · 2026Review
- 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
- Defining the impact of Getah virus envelope protein glycosylation site mutations on viral replication, host adaptation, virulence, and immune evasion.PLoS pathogens · 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
- Three positively charged binding sites on the eastern equine encephalitis virus E2 glycoprotein coordinate heparan sulfate- and protein receptor-dependent infection.Nature communications · 2025Article
- Basic patches on the E2 glycoprotein of eastern equine encephalitis virus influence viral vascular clearance and dissemination in mice.Journal of virology · 2025Article
- Attenuation Profile and Molecular Characterization of a High-Passaged Attenuated Getah Virus Strain.Transboundary and emerging diseases · 2025Article
- Insights into mosquito-borne arbovirus receptors.Cell insight · 2024Review
- Phagocyte-expressed glycosaminoglycans promote capture of alphaviruses from the blood circulation in a host species-specific manner.PNAS nexus · 2024Article
- Novel approaches for the rapid development of rationally designed arbovirus vaccines.One health (Amsterdam, Netherlands) · 2023Article
- Entry receptors - the gateway to alphavirus infection.The Journal of clinical investigation · 2023Review
- Article
- 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
- Natural and Recombinant SARS-CoV-2 Isolates Rapidly EvolveJournal of virology · 2021Article
- Alphavirus-Induced Membrane Rearrangements during Replication, Assembly, and Budding.Pathogens (Basel, Switzerland) · 2021Review
- Alphavirus Virulence Determinants.Pathogens (Basel, Switzerland) · 2021Review
- The Structural Biology of Eastern Equine Encephalitis Virus, an Emerging Viral Threat.Pathogens (Basel, Switzerland) · 2021Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Cell culture-adapted laboratory strains of Sindbis virus (SB) exhibit efficient initial attachment to cell surface heparan sulfate (HS) receptors. In contrast, non-cell-adapted strains, such as the SB consensus sequence virus TR339, interact weakly with HS and cell surfaces. Regardless of their HS binding phenotype, most SB strains do not cause fatal disease in adult mice, whether inoculated subcutaneously (s.c.) or intracranially (i.c.). However, laboratory strains of SB can be rendered neurovirulent for adult mice by introduction of a glutamine (Gln)-to-histidine (His) mutation at position 55 of the E2 envelope glycoprotein. In the current work, we have determined that E2 His 55-containing viruses require a second-site mutation (Glu to Lys) at E2 position 70 that confers efficient HS binding in order to exhibit virulence for adult mice and that virulence is correlated with very high infectivity for many cell types. Furthermore, introduction of E2 Lys 70 or certain other HS-binding mutations alone also increased morbidity and/or mortality over that of TR339 for older mice inoculated i.c. However, all viruses containing single HS-binding mutations were attenuated in s.c. inoculated suckling mice in comparison with TR339. These results suggest that HS binding may attenuate viral disease that is dependent on high-titer viremia; however, efficient cell attachment through HS binding can increase virulence, presumably through enhancing the replication of SB within specific host tissues such as the brain.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.