Peromyscus leucopus mouse brain transcriptome response to Powassan virus infection

J Neurovirol. 2018 Feb;24(1):75-87. doi: 10.1007/s13365-017-0596-y. Epub 2017 Nov 16.

Abstract

Powassan virus (POWV) is a tick-borne Flavivirus responsible for life-threatening encephalitis in North America and some regions of Russia. The ticks that have been reported to transmit the virus belong to the Ixodes species, and they feed on small-to-medium-sized mammals, such as Peromyscus leucopus mice, skunks, and woodchucks. We previously developed a P. leucopus mouse model of POWV infection, and the model is characterized by a lack of clinical signs of disease following intraperitoneal or intracranial inoculation. However, intracranial inoculation results in mild subclinical encephalitis from 5 days post infection (dpi), but the encephalitis resolves by 28 dpi. We used RNA sequencing to profile the P. leucopus mouse brain transcriptome at different time points after intracranial challenge with POWV. At 24 h post infection, 42 genes were significantly differentially expressed and the number peaked to 232 at 7 dpi before declining to 31 at 28 dpi. Using Ingenuity Pathway Analysis, we determined that the genes that were significantly expressed from 1 to 15 dpi were mainly associated with interferon signaling. As a result, many interferon-stimulated genes (ISGs) were upregulated. Some of the ISGs include an array of TRIMs (genes encoding tripartite motif proteins). These results will be useful for the identification of POWV restriction factors.

Keywords: Brain transcriptome; Differential gene expression; Interferon signaling; Peromyscus lecuopus mouse; Powassan virus; Tick-borne flavivirus.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Brain / virology*
  • Disease Models, Animal
  • Encephalitis Viruses, Tick-Borne / genetics
  • Encephalitis Viruses, Tick-Borne / pathogenicity
  • Encephalitis, Tick-Borne / genetics*
  • Encephalitis, Tick-Borne / immunology
  • Encephalitis, Tick-Borne / virology
  • Gene Expression Regulation
  • Gene Regulatory Networks
  • High-Throughput Nucleotide Sequencing
  • Host-Pathogen Interactions / genetics
  • Host-Pathogen Interactions / immunology
  • Injections, Intraventricular
  • Interferon Regulatory Factors / genetics*
  • Interferon Regulatory Factors / immunology
  • Ixodes / virology
  • Peromyscus / genetics
  • Peromyscus / immunology
  • Peromyscus / virology*
  • Signal Transduction
  • Transcriptome*
  • Tripartite Motif Proteins / genetics*
  • Tripartite Motif Proteins / immunology

Substances

  • Interferon Regulatory Factors
  • Tripartite Motif Proteins