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Journal of virology2005; 79(14); 9128-9133; doi: 10.1128/JVI.79.14.9128-9133.2005

Envelope glycoprotein mutations mediate equine amplification and virulence of epizootic venezuelan equine encephalitis virus.

Abstract: Epidemics of Venezuelan equine encephalitis (VEE) result from high-titer equine viremia of IAB and IC subtype viruses that mediate increased mosquito transmission and spillover to humans. Previous genetic studies suggest that mutations in the E2 envelope glycoprotein allow relatively viremia-incompetent, enzootic subtype ID strains to adapt for equine replication, leading to VEE emergence. To test this hypothesis directly, chimeric VEEV strains containing the genetic backbone of enzootic subtype ID strains and the partial envelope glycoprotein genes of epizootic subtype IC and IAB strains, as well as reciprocal chimeras, were used for experimental infections of horses. Insertion of envelope genes from two different, closely related enzootic subtype ID strains into the epizootic backbones resulted in attenuation, demonstrating that the epizootic envelope genes are necessary for the equine-virulent and viremia-competent phenotypes. The partial epizootic envelope genes introduced into an enzootic ID backbone were sufficient to generate the virulent, viremia-competent equine phenotype. These results indicate that a small number of envelope gene mutations can generate an equine amplification-competent, epizootic VEEV from an enzootic progenitor and underscore the limitations of small animal models for evaluating and predicting the epizootic phenotype.
Publication Date: 2005-07-05 PubMed ID: 15994807PubMed Central: PMC1168750DOI: 10.1128/JVI.79.14.9128-9133.2005Google Scholar: Lookup
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  • Journal Article
  • Research Support
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  • Extramural
  • Research Support
  • Non-U.S. Gov't
  • Research Support
  • U.S. Gov't
  • P.H.S.

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The study discusses the role of mutations in the E2 envelope glycoprotein in allowing subtype ID strains of Venezuelan equine encephalitis (VEE) virus to adapt for equine replication, thereby leading to VEE emergence. The researchers created chimeric VEEV strains using these mutations and conducted experimental infections in horses. It was found that the mutations were necessary for the virus’s virulence and competence for viremia.

Methods and Materials

  • The researchers began by constructing chimeric VEEV strains. These strains had the genetic backbone of enzootic subtype ID strains and part of the envelope glycoprotein genes of epizootic subtype IC and IAB strains.
  • Additional chimeras were made by inserting the envelope genes from two distinct enzootic subtype ID strains into the epizootic backbones.
  • These chimeras were then used to infect horses in a controlled experiment. This allowed the researchers to monitor and analyze how the virus and its mutations interacted with the equine immune system and affected the disease’s progression.

Results and Discussion

  • The results of the experiments showed a clear link between the envelope glycoprotein mutations and the virus’s virulence (ability to cause severe illness) and viremia competence (ability to replicate within the host and produce high viral loads).
  • Specifically, they found that the introduction of envelope genes from enzootic ID strains into the epizootic strain resulted in an attenuated (weaker) form of the virus. This provided strong evidence that the envelope mutations are crucial for the virus’s ability to replicate within horses and cause severe illness.
  • Conversely, the introduction of partial epizootic envelope genes into the enzootic ID strain was sufficient to transform it into a virulent, viremia-competent form of the virus.
  • Therefore, the researchers concluded that a small number of envelope gene mutations can significantly alter the VEEV virus’s behavior and allow it to cause epidemics.

Implications and Conclusion

  • This research underscores the key role played by genetic mutations in viral evolution and emergence of new infectious diseases. Specifically, the findings highlight how relatively minor genetic changes can drastically affect a virus’s ability to replicate and cause disease within a new host species.
  • Despite the evident success of this investigation, the authors also pointed out the limitations of using small animal models to predict a virus’s behavior in larger organisms, highlighting the need for further research in this area.

Cite This Article

APA
Greene IP, Paessler S, Austgen L, Anishchenko M, Brault AC, Bowen RA, Weaver SC. (2005). Envelope glycoprotein mutations mediate equine amplification and virulence of epizootic venezuelan equine encephalitis virus. J Virol, 79(14), 9128-9133. https://doi.org/10.1128/JVI.79.14.9128-9133.2005

Publication

ISSN: 0022-538X
NlmUniqueID: 0113724
Country: United States
Language: English
Volume: 79
Issue: 14
Pages: 9128-9133

Researcher Affiliations

Greene, Ivorlyne P
  • Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, TX 77555-0609, USA.
Paessler, Slobodan
    Austgen, Laura
      Anishchenko, Michael
        Brault, Aaron C
          Bowen, Richard A
            Weaver, Scott C

              MeSH Terms

              • Animals
              • Chlorocebus aethiops
              • Cricetinae
              • Encephalitis Virus, Venezuelan Equine / pathogenicity
              • Encephalomyelitis, Venezuelan Equine / etiology
              • Horses
              • Mutation
              • Vero Cells
              • Viral Envelope Proteins / physiology
              • Viremia / virology
              • Virulence

              Grant Funding

              • R03 AI107536 / NIAID NIH HHS
              • K08 AI05949 / NIAID NIH HHS
              • AI10984 / NIAID NIH HHS
              • T32 AI107536 / NIAID NIH HHS
              • AI39800 / NIAID NIH HHS
              • T32 AI-107526 / NIAID NIH HHS
              • 417760 / PHS HHS
              • AI38807 / NIAID NIH HHS

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