Publications by authors named "W B Klimstra"
Eastern equine encephalitis virus (EEEV) is an arthropod-borne, positive-sense RNA alphavirus posing a substantial threat to public health. Unlike similar viruses such as SARS-CoV-2, EEEV replicates efficiently in neurons, producing progeny viral particles as soon as 3-4 hours post-infection. EEEV infection, which can cause severe encephalitis with a human mortality rate surpassing 30%, has no licensed, targeted therapies, leaving patients to rely on supportive care.
View Article and Find Full Text PDFNaturally circulating strains of eastern equine encephalitis virus (EEEV) bind heparan sulfate (HS) receptors and this interaction has been linked to its neurovirulence. Previous studies associated EEEV-HS interactions with three positively charged amino acid clusters on the E2 glycoprotein. One of these sites has recently been reported to be critical for binding EEEV to very-low-density lipoprotein receptor (VLDLR), an EEEV receptor protein.
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- VLDLR has been identified as a receptor for several alphaviruses, including Western equine encephalitis virus (WEEV), and may play a role in their infection process.
- Research shows that mice lacking VLDLR have reduced susceptibility to WEEV, EEEV, and Semliki Forest virus (SFV), indicating its importance in alphavirus pathogenesis.
- The findings suggest that targeting VLDLR could be a potential strategy for developing treatments against various alphavirus infections.
Since SARS-CoV-2 emerged in late 2019, it spread from China to the rest of the world. An initial concern was the potential for vaccine- or antibody-dependent enhancement (ADE) of disease as had been reported with other coronaviruses. To evaluate this, we first developed a ferret model by exposing ferrets to SARS-CoV-2 by either mucosal inoculation (intranasal/oral/ocular) or inhalation using a small particle aerosol.
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- The study explores how the levels of viremia (virus in the bloodstream) affect arbovirus transmission and disease severity, particularly focusing on the relationship between viral variants and glycosaminoglycan (GAG) interactions.
- Using an in vivo model, researchers found that GAG-binding viruses are cleared from the bloodstream faster than non-GAG-binding ones, but the rate of clearance varies by virus type and relies on phagocytes for some variants.
- The findings highlight the role of GAGs in viral clearance and suggest that different species, like birds and mice, may interact with viruses differently based on their unique GAG structures, impacting arbovirus spread and ecology.