AI Article Synopsis

  • 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.

Article Abstract

The magnitude and duration of vertebrate viremia are critical determinants of arbovirus transmission, geographic spread, and disease severity-yet, mechanisms determining arbovirus viremia levels are poorly defined. Previous studies have drawn associations between in vitro virion-glycosaminoglycan (GAG) interactions and in vivo clearance kinetics of virions from blood circulation. From these observations, it is commonly hypothesized that GAG-binding virions are rapidly removed from circulation due to ubiquitous expression of GAGs by vascular endothelial cells, thereby limiting viremia. Using an in vivo model for viremia, we compared the vascular clearance of low and enhanced GAG-binding viral variants of chikungunya, eastern- (EEEV), and Venezuelan- (VEEV) equine encephalitis viruses. We find GAG-binding virions are more quickly removed from circulation than their non-GAG-binding variant; however individual clearance kinetics vary between GAG-binding viruses, from swift (VEEV) to slow removal from circulation (EEEV). Remarkably, we find phagocytes are required for efficient vascular clearance of some enhanced GAG-binding virions. Moreover, transient depletion of vascular heparan sulfate impedes vascular clearance of only some GAG-binding viral variants and in a phagocyte-dependent manner, implying phagocytes can mediate vascular GAG-virion interactions. Finally, in direct contrast to mice, we find enhanced GAG-binding EEEV is resistant to vascular clearance in avian hosts, suggesting the existence of species-specificity in virion-GAG interactions. In summary, these data support a role for GAG-mediated clearance of some viral particles from the blood circulation, illuminate the potential of blood-contacting phagocytes as a site for GAG-virion binding, and suggest a role for species-specific GAG structures in arbovirus ecology.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10978064PMC
http://dx.doi.org/10.1093/pnasnexus/pgae119DOI Listing

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