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PloS one2011; 6(10); e24371; doi: 10.1371/journal.pone.0024371

Gene expression analysis in the thalamus and cerebrum of horses experimentally infected with West Nile virus.

Abstract: Gene expression associated with West Nile virus (WNV) infection was profiled in the central nervous system of horses. Pyrosequencing and library annotation was performed on pooled RNA from the CNS and lymphoid tissues on horses experimentally infected with WNV (vaccinated and naïve) and non-exposed controls. These sequences were used to create a custom microarray enriched for neurological and immunological sequences to quantitate gene expression in the thalamus and cerebrum of three experimentally infected groups of horses (naïve/WNV exposed, vaccinated/WNV exposed, and normal).From the sequenced transcriptome, 41,040 sequences were identified by alignment against five databases. 31,357 good sequence hits (e<10(-4)) were obtained with 3.1% of the sequences novel to the equine genome project. Sequences were compared to human expressed sequence tag database, with 31,473 equine sequences aligning to human sequences (69.27% contigs, 78.13% seed contigs, 80.17% singlets). This indicated a high degree of sequence homology between human and equine transcriptome (average identity 90.17%).Significant differences (p<0.05) in gene expression were seen due to virus exposure (9,020), survival (7,395), and location (7,649). Pathways analysis revealed many genes that mapped to neurological and immunological categories. Involvement of both innate and adaptive components of immunity was seen, with higher levels of expression correlating with survival. This was highlighted by increased expression of suppressor of cytokine signaling 3 in horses exposed to WNV which functions to suppress innate immunity. Pentraxin 3 was most increased in expression for all horses exposed to WNV.Neurological pathways that demonstrated the greatest changes in gene expression included neurotransmitter and signaling pathways. Decreased expression of transcripts in both the glutamate and dopamine signaling pathways was seen in horses exposed to WNV, providing evidence of possible glutamate excitotoxicity and clinical signs associated with decreased dopamine. Many transcripts mapped to non-infectious neurological disease functions, including mental disorders and degenerative neuropathies.
Publication Date: 2011-10-04 PubMed ID: 21991302PubMed Central: PMC3186766DOI: 10.1371/journal.pone.0024371Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

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 article looks into the gene expression patterns in horses that have been experimentally infected with West Nile virus (WNV). It uncovers that WNV exposure, survival and location resulted in significant differences in gene expressions, most notably neurological and immunological pathways.

Methodology

  • The research used pyrosequencing and library annotation on pooled RNA samples from the central nervous system (CNS) and lymphoid tissues of horses experimentally infected with WNV and non-exposed controls. The horses subjected to experimental infection were either vaccinated prior to exposure or were completely naive.
  • A custom microarray was created from the sequenced transcriptome to quantify gene expression in the thalamus and cerebrum of the infected horses.
  • These sequences were then cross-referenced against five databases to identify and analyze any relevant hits, with a close attention to ones that might be novel to the equine genome project and their homology to human sequences.

Results

  • The profiled gene expression resulted in identifying 41,040 sequences. After comparing these to various databases, the researchers found 31,357 good sequence hits, among which 3.1% were novel to the equine genome project.
  • The sequences showed a high level of homology to human transcriptome (average identity 90.17%). This means that the gene expressions in horses infected with WNV have significant similarities with humans.
  • Significant differences in gene expression were observed due to a few factors such as virus exposure (9,020), survival (7,395), and location (7,649).
  • Both innate and adaptive immunity components were found to be involved, with higher levels of expression correlating with survival. The expression of suppressor of cytokine signaling 3 was increased in horses exposed to WNV, suggesting it has a role in suppressing innate immunity. Likewise, Pentraxin 3 showed the most increase in expression in all horses exposed to WNV.

Conclusion

  • The neurological pathways showing the greatest changes in gene expression included neurotransmitter and signaling pathways. There was decreased expression of transcripts in both the glutamate and dopamine signaling pathways in horses exposed to WNV, which suggests a possible occurrence of glutamate excitotoxicity and clinical signs associated with decreased dopamine.
  • Additionally, many transcripts were found to map to non-infectious neurological disease functions, including mental disorders and degenerative neuropathies, potentially suggesting a broader effect of the WNV on the horses’ neurological system beyond the infection itself.

Cite This Article

APA
Bourgeois MA, Denslow ND, Seino KS, Barber DS, Long MT. (2011). Gene expression analysis in the thalamus and cerebrum of horses experimentally infected with West Nile virus. PLoS One, 6(10), e24371. https://doi.org/10.1371/journal.pone.0024371

Publication

ISSN: 1932-6203
NlmUniqueID: 101285081
Country: United States
Language: English
Volume: 6
Issue: 10
Pages: e24371
PII: e24371

Researcher Affiliations

Bourgeois, Melissa A
  • Department of Infectious Diseases and Pathology, University of Florida College of Veterinary Medicine, Gainesville, Florida, United States of America.
Denslow, Nancy D
    Seino, Kathy S
      Barber, David S
        Long, Maureen T

          MeSH Terms

          • Animals
          • Cerebrum / metabolism
          • Expressed Sequence Tags
          • Gene Expression Profiling
          • Gene Expression Regulation
          • Horses / genetics
          • Horses / immunology
          • Horses / virology
          • Humans
          • Interleukin-15 / biosynthesis
          • Molecular Sequence Annotation
          • Oligonucleotide Array Sequence Analysis
          • RNA, Messenger / genetics
          • RNA, Messenger / metabolism
          • Receptors, Dopamine / metabolism
          • Receptors, Glutamate / genetics
          • Receptors, Glutamate / metabolism
          • Reproducibility of Results
          • Sequence Analysis, DNA
          • Signal Transduction / genetics
          • Signal Transduction / immunology
          • Thalamus / metabolism
          • Transcriptome
          • West Nile Fever / genetics
          • West Nile Fever / immunology
          • West Nile Fever / pathology
          • West Nile Fever / virology
          • West Nile virus / physiology

          Conflict of Interest Statement

          The authors have declared that no competing interests exist.

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