Identification of Cellular Receptors and Receptor Shifts in the Submergence of a Virulent Arbovirus: Western Equine Encephalitis Virus

Core Concepts

Identification of cellular receptors PCDH10, VLDLR, and ApoER2 for highly virulent ancestral strains of Western Equine Encephalitis Virus, and the loss of PCDH10 binding in a contemporary strain, suggesting viral adaptation to a main reservoir host.

Abstract

The content discusses the identification of cellular receptors for the arbovirus Western Equine Encephalitis Virus (WEEV) and the changes in receptor binding observed between ancestral and contemporary strains of the virus.

Key highlights:

• WEEV is an arbovirus that caused major outbreaks of encephalitis in humans and horses in the early 20th century, but the frequency of outbreaks has since decreased.
• The authors identified three cellular receptors for highly virulent ancestral WEEV strains isolated in the 1930s and 1940s: protocadherin 10 (PCDH10), very low-density lipoprotein receptor (VLDLR), and apolipoprotein E receptor 2 (ApoER2).
• However, a contemporary WEEV strain has lost the ability to recognize the mammalian receptor PCDH10, while retaining the ability to bind avian receptors, suggesting viral adaptation to a main reservoir host during enzootic circulation.
• PCDH10 was shown to support WEEV infection of primary mouse cortical neurons, and a soluble form of PCDH10 protected mice from lethal WEEV challenge.
• The findings have implications for the development of medical countermeasures and risk assessment for the re-emergence of highly virulent WEEV strains.

Stats

WEEV strains isolated in the 1930s and 1940s could bind to human PCDH10, VLDLR, and ApoER2 receptors.
A contemporary WEEV strain has lost the ability to recognize mammalian PCDH10 receptor.
PCDH10 supports WEEV infection of primary mouse cortical neurons.
Administration of a soluble form of PCDH10 protected mice from lethal WEEV challenge.

Quotes

"PCDH10 supports WEEV E2–E1 glycoprotein-mediated infection of primary mouse cortical neurons, and administration of a soluble form of PCDH10 protects mice from lethal WEEV challenge."
"Our results have implications for the development of medical countermeasures and for risk assessment for re-emerging WEEV strains."

Key Insights Distilled From

Shifts in receptors during submergence of an encephalitic arbovirus - Nature

by Wanyu Li,Jes... at www.nature.com 07-24-2024

https://www.nature.com/articles/s41586-024-07740-2

Deeper Inquiries

What other cellular receptors or host factors might be involved in WEEV infection and adaptation?

Apart from protocadherin 10 (PCDH10), very low-density lipoprotein receptor (VLDLR) and apolipoprotein E receptor 2 (ApoER2) have been identified as cellular receptors for Western equine encephalitis virus (WEEV). These receptors play crucial roles in facilitating WEEV infection and adaptation. Additionally, other host factors such as cell surface proteins, lipid receptors, and specific cellular signaling pathways may also be involved in WEEV infection and adaptation. Further research is needed to comprehensively understand the full spectrum of cellular receptors and host factors that contribute to WEEV infection dynamics.

How do the receptor binding changes in WEEV relate to changes in virulence and pathogenicity over time?

The receptor binding changes in WEEV are closely linked to alterations in virulence and pathogenicity over time. The ability of WEEV strains to bind to specific cellular receptors like PCDH10, VLDLR, and ApoER2 influences their infectivity and pathogenic potential. The shift in receptor recognition from mammalian PCDH10 to avian receptors in contemporary WEEV strains indicates an adaptation to different host reservoirs, potentially impacting the virus's virulence in mammalian hosts. These changes in receptor binding patterns can modulate the efficiency of viral entry, replication, and spread within the host, ultimately influencing the severity of disease outcomes. Understanding these receptor binding changes is crucial for elucidating the mechanisms underlying the evolution of WEEV virulence and pathogenicity.

What insights can the WEEV receptor shifts provide for understanding the evolution and ecology of other arboviruses?

The WEEV receptor shifts offer valuable insights into the evolution and ecology of other arboviruses by highlighting the dynamic interplay between viral receptors and host factors. The ability of WEEV strains to adapt to different host reservoirs by altering their receptor recognition patterns underscores the importance of host specificity in arbovirus transmission and pathogenesis. These receptor shifts also demonstrate the selective pressures that drive viral evolution, leading to changes in virulence and host range over time. By studying the receptor interactions of WEEV and how they influence viral fitness, researchers can gain a deeper understanding of the evolutionary mechanisms that shape the emergence and spread of arboviruses, providing valuable information for the surveillance and control of other arboviral diseases.