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Peromyscus leucopus mouse brain transcriptome response to Powassan virus infection
Luwanika Mlera1, Kimberly Meade-White2, Eric Dahlstrom3
1Biology of Vector-Borne Viruses Section, Laboratory of Virology, Rocky Mountain Laboratories, NIAID/NIH, Hamilton, MT, 59840, USA. Luwanika.Mlera@nih.gov.
Journal of Neurovirology
|November 18, 2017
Summary
Powassan virus (POWV) infection in mice triggers interferon signaling and upregulates interferon-stimulated genes (ISGs), including TRIMs, in the brain. This provides insights into POWV restriction factors and host responses to tick-borne Flavivirus encephalitis.
Area of Science:
- Virology
- Neuroscience
- Immunology
Background:
- Powassan virus (POWV) is a tick-borne Flavivirus causing severe encephalitis in North America and Russia.
- Ixodes ticks transmit POWV, often feeding on small mammals like Peromyscus leucopus mice.
- A P. leucopus mouse model exhibits subclinical encephalitis following intracranial POWV inoculation.
Purpose of the Study:
- To investigate the host's brain gene expression profile during Powassan virus infection.
- To identify key molecular pathways and genes involved in the host response to POWV.
- To discover potential Powassan virus restriction factors.
Main Methods:
- Intracranial inoculation of P. leucopus mice with Powassan virus.
- RNA sequencing of mouse brain tissue at multiple time points post-infection (24 hours, 7 days, 28 days).
- Ingenuity Pathway Analysis (IPA) to interpret differentially expressed genes.
Main Results:
- Significant differential gene expression observed, peaking at 7 days post-infection.
- Interferon signaling pathways were predominantly activated between 1 and 15 days post-infection.
- Numerous interferon-stimulated genes (ISGs), including tripartite motif (TRIM) genes, were upregulated.
Conclusions:
- Powassan virus infection induces a robust interferon response in the mouse brain.
- Upregulated ISGs, particularly TRIMs, may play a role in restricting viral replication.
- These findings contribute to understanding POWV pathogenesis and identifying host restriction factors.
