Comparative pathology study of Venezuelan, eastern, and western equine encephalitis viruses in non-human primates.
Abstract: Venezuelan, eastern, and western equine encephalitis viruses (VEEV, EEEV, and WEEV) are mosquito-borne viruses in the Americas that cause central nervous system (CNS) disease in humans and equids. In this study, we directly characterized the pathogenesis of VEEV, EEEV, and WEEV in cynomolgus macaques following subcutaneous exposure because this route more closely mimics natural infection via mosquito transmission or by an accidental needle stick. Our results highlight how EEEV is significantly more pathogenic compared to VEEV similarly to what is observed in humans. Interestingly, EEEV appears to be just as neuropathogenic by subcutaneous exposure as it was in previously completed aerosol exposure studies. In contrast, subcutaneous exposure of cynomolgus macaques with WEEV caused limited disease and is contradictory to what has been reported for aerosol exposure. Several differences in viremia, hematology, or tissue tropism were noted when animals were exposed subcutaneously compared to prior aerosol exposure studies. This study provides a more complete picture of the pathogenesis of the encephalitic alphaviruses and highlights how further defining the neuropathology of these viruses could have important implications for the development of medical countermeasures for the neurovirulent alphaviruses.
Published by Elsevier B.V.
Publication Date: 2020-08-02 PubMed ID: 32755661DOI: 10.1016/j.antiviral.2020.104875Google Scholar: Lookup
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- Comparative Study
- Journal Article
Summary
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The study examines the pathology of Venezuelan, eastern, and western equine encephalitis viruses in non-human primates, specifically cynomolgus macaques, through a route that closely mimics natural infection. The results show differences in the pathogenic nature of the three encephalitic viruses, with the eastern variety proving significantly more detrimental than the Venezuelan one, a pattern also observed in humans.
Methodology
- The researchers studied the pathogenesis of Venezuelan, eastern, and western equine encephalitis viruses (VEEV, EEEV, and WEEV) in non-human primates, particularly cynomolgus macaques.
- The way of exposure to the viruses was made to mimic natural infection, through subcutaneous exposure, imitating a mosquito transmission or needle stick accident closely.
Findings
- One of the significant findings of the study is that EEEV or Eastern Encephalitis Virus is a lot more pathogenic compared to VEEV (Venezuelan equine encephalitis viruses). This finding mirrors the pattern observed in human infections, thus, validating its accuracy.
- When the EEEV was transmitted subcutaneously, its neuropathogenic effects were found to be similar to those observed in aerosol exposure studies, i.e., the method of transmission doesn’t alter its pathogenesis.
- On the other hand, the WEEV or Western Encephalitis Virus presented limited disease symptoms when introduced subcutaneously into the macaques. This contradicts previous findings using aerosol exposure, indicating that the exposure method might influence the pathogenesis of this virus.
- The researchers observed differences in viremia (the presence of viruses in the blood), hematology (study of blood), and tissue tropism (the cells and tissues of a host which support growth of a particular virus) when animals were exposed subcutaneously compared to prior aerosol exposure studies.
Implications
- By presenting a more comprehensive understanding of the pathogenesis of the encephalitic alphaviruses, the study aids in the development of medical countermeasures against these neurovirulent viruses.
- The findings underline the importance of further defining the neuropathology of these viruses to improve treatments and preventative strategies in humans and equids, largely horses, donkeys, and zebras.
Cite This Article
APA
Smith DR, Schmaljohn CS, Badger C, Ostrowski K, Zeng X, Grimes SD, Rayner JO.
(2020).
Comparative pathology study of Venezuelan, eastern, and western equine encephalitis viruses in non-human primates.
Antiviral Res, 182, 104875.
https://doi.org/10.1016/j.antiviral.2020.104875 Publication
Researcher Affiliations
- United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, 21702, MD, USA. Electronic address: darci.r.smith.civ@mail.mil.
- United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, 21702, MD, USA.
- United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, 21702, MD, USA.
- United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, 21702, MD, USA.
- United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, 21702, MD, USA.
- Southern Research, Birmingham, 35255, AL, USA.
- University of South Alabama, Mobile, 36688, AL, USA.
MeSH Terms
- Animals
- Antibodies, Neutralizing / blood
- Antibodies, Viral / blood
- Encephalitis Virus, Eastern Equine / pathogenicity
- Encephalitis Virus, Venezuelan Equine / pathogenicity
- Encephalitis Virus, Western Equine / pathogenicity
- Encephalomyelitis, Equine / pathology
- Encephalomyelitis, Venezuelan Equine / pathology
- Female
- Macaca fascicularis / virology
- Male
- Virus Replication
Citations
This article has been cited 7 times.- Reyna RA, Weaver SC. Sequelae and Animal Modeling of Encephalitic Alphavirus Infections.. Viruses 2023 Jan 28;15(2).
- Skidmore AM, Bradfute SB. The life cycle of the alphaviruses: From an antiviral perspective.. Antiviral Res 2023 Jan;209:105476.
- Williams JA, Long SY, Zeng X, Kuehl K, Babka AM, Davis NM, Liu J, Trefry JC, Daye S, Facemire PR, Iversen PL, Bavari S, Pitt ML, Nasar F. Eastern equine encephalitis virus rapidly infects and disseminates in the brain and spinal cord of cynomolgus macaques following aerosol challenge.. PLoS Negl Trop Dis 2022 May;16(5):e0010081.
- Suschak JJ, Bixler SL, Badger CV, Spik KW, Kwilas SA, Rossi FD, Twenhafel N, Adams ML, Shoemaker CJ, Spiegel E, Hooper JW. A DNA vaccine targeting VEE virus delivered by needle-free jet-injection protects macaques against aerosol challenge.. NPJ Vaccines 2022 Apr 22;7(1):46.
- Kafai NM, Diamond MS, Fox JM. Distinct Cellular Tropism and Immune Responses to Alphavirus Infection.. Annu Rev Immunol 2022 Apr 26;40:615-649.
- May Fulton C, Bailey WJ. Live Viral Vaccine Neurovirulence Screening: Current and Future Models.. Vaccines (Basel) 2021 Jun 30;9(7).
- Barraza SJ, Sindac JA, Dobry CJ, Delekta PC, Lee PH, Miller DJ, Larsen SD. Synthesis and biological activity of conformationally restricted indole-based inhibitors of neurotropic alphavirus replication: Generation of a three-dimensional pharmacophore.. Bioorg Med Chem Lett 2021 Aug 15;46:128171.
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