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Home / Equine Research Bank / Am J Trop Med Hyg / Eastern Equine Encephalitis Virus Diversity in Massachusetts...
The American journal of tropical medicine and hygiene2023; 109(2); 387-396; doi: 10.4269/ajtmh.23-0047

Eastern Equine Encephalitis Virus Diversity in Massachusetts Patients, 1938-2020.

Abstract: Eastern equine encephalitis virus (EEEV) is a relatively little-studied alphavirus that can cause devastating viral encephalitis, potentially leading to severe neurological sequelae or death. Although case numbers have historically been low, outbreaks have been increasing in frequency and scale since the 2000 s. It is critical to investigate EEEV evolutionary patterns, especially within human hosts, to understand patterns of emergence, host adaptation, and within-host evolution. To this end, we obtained formalin-fixed paraffin-embedded tissue blocks from discrete brain regions from five contemporary (2004-2020) patients from Massachusetts, confirmed the presence of EEEV RNA by in situ hybridization (ISH) staining, and sequenced viral genomes. We additionally sequenced RNA from scrapings of historical slides made from brain sections of a patient in the first documented EEE outbreak in humans in 1938. ISH staining revealed the presence of RNA in all contemporary samples, and quantification loosely correlated with the proportion of EEEV reads in samples. Consensus EEEV sequences were generated for all six patients, including the sample from 1938; phylogenetic analysis using additional publicly available sequences revealed clustering of each study sample with like sequences from a similar region, whereas an intrahost comparison of consensus sequences between discrete brain regions revealed minimal changes. Intrahost single nucleotide variant (iSNV) analysis of four samples from two patients revealed the presence of tightly compartmentalized, mostly nonsynonymous iSNVs. This study contributes critical primary human EEEV sequences, including a historic sequence as well as novel intrahost evolution findings, contributing substantially to our understanding of the natural history of EEEV infection in humans.
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Publication Date: 2023-06-20 PubMed ID: 37339758PubMed Central: PMC10397450DOI: 10.4269/ajtmh.23-0047Google Scholar: Lookup
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  • Research Support
  • N.I.H.
  • Extramural

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 research investigates the evolution of Eastern Equine Encephalitis Virus (EEEV) in human hosts and its impact, especially in Massachusetts between 1938-2020. Evidence of the virus was confirmed via in situ hybridization (ISH) staining and viral genomes sequencing from brain tissue samples of diseased individuals.

Research Procedure

  • The researchers obtained formalin-fixed paraffin-embedded brain tissue blocks from five patients who succumbed to EEEV between 2004-2020.
  • Using in situ hybridization (ISH) staining, they confirmed the presence of EEEV RNA in the brain tissues.
  • Sequencing of the viral genomes ensued.
  • In addition, they sequenced RNA from scrapings of historic slides made from brain sections of a patient involved in the first documented EEEV outbreak in humans in 1938.

Findings

  • ISH staining revealed the presence of RNA in all samples taken from the contemporary period (2004-2020).
  • The intensity of the ISH staining loosely correlated with the proportion of EEEV reads in the samples, further confirming presence of the virus.
  • Consensus EEEV sequences were generated for all six patients, including the sample from 1938.
  • A phylogenetic analysis being carried out using additional publicly available sequences showed each study sample clustering with like sequences from the same or similar regions. Minimal changes were noted between consensus sequences in different brain regions from the same host.
  • Intrahost single nucleotide variant (iSNV) analysis of four samples from two patients showed tightly compartmentalized, mostly nonsynonymous iSNVs.

Significance of the Research

  • The research offers a critical historical perspective to the sequence and evolution of EEEV in humans.
  • It also presents novel findings on intrahost evolution, which will prove instrumental in understanding EEEV’s patterns of emergence and adaptation to human hosts.
  • The study fills critical knowledge gaps in the study of this relatively understudied virus, whose outbreaks have been on a increase since the early 2000s.

Cite This Article

APA
Langsjoen RM, Key A, Shariatzadeh N, Jackson CR, Mahmood F, Arkun K, Alexandrescu S, Solomon IH, Piantadosi A. (2023). Eastern Equine Encephalitis Virus Diversity in Massachusetts Patients, 1938-2020. Am J Trop Med Hyg, 109(2), 387-396. https://doi.org/10.4269/ajtmh.23-0047

Publication

The American journal of tropical medicine and hygiene
ISSN: 1476-1645
NlmUniqueID: 0370507
Country: United States
Language: English
Volume: 109
Issue: 2
Pages: 387-396

Researcher Affiliations

Langsjoen, Rose M
  • Department of Pathology, Emory University School of Medicine, Atlanta, Georgia.
Key, Autum
  • Department of Pathology, Emory University School of Medicine, Atlanta, Georgia.
Shariatzadeh, Nima
  • Department of Pathology, Emory University School of Medicine, Atlanta, Georgia.
Jackson, Christopher R
  • Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Mahmood, Faisal
  • Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Arkun, Knarik
  • Department of Pathology and Laboratory Medicine, Tufts Medical Center, Boston, Massachusetts.
Alexandrescu, Sanda
  • Department of Pathology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.
Solomon, Isaac H
  • Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Piantadosi, Anne
  • Department of Pathology, Emory University School of Medicine, Atlanta, Georgia.
  • Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia.

MeSH Terms

  • Humans
  • Animals
  • Horses / genetics
  • Encephalitis Virus, Eastern Equine / genetics
  • Phylogeny
  • Encephalomyelitis, Equine / epidemiology
  • Massachusetts / epidemiology
  • RNA, Viral / genetics

Grant Funding

  • P30 CA006516 / NCI NIH HHS
  • R21 NS119660 / NINDS NIH HHS

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