Researchers at Rockefeller University, led by Charles M. Rice and publishing in the journal Immunity, report that the brain begins to prepare for viral attack within hours after an infection far from the head. Using mouse models, the team injected West Nile virus (WNV) into footpads and examined brains at several time points. They found interferon-stimulated antiviral genes (ISGs) activated in the brain even though virus was not detectable there; virus-associated molecules in the infected foot were enough to trigger the response.
To map how signals reach the central nervous system, scientists tested a range of pathogen-associated molecular patterns (PAMPs) in the footpad. The brain reacted specifically to different PAMPs and activated distinct transcriptomic programs. When mice received poly(I:C) in the footpad and were then infected directly in the brain, survival improved. The protection applied to WNV, related Powassan virus and to unrelated herpes simplex in these experiments.
Further experiments showed poly(I:C) provoked a systemic type I interferon response that induced ISGs in brain microvascular endothelial cells (BMECs) that form the blood-brain barrier (BBB). Analyses suggest BMECs relay the signal into the CNS and prompt innate immune cells such as microglia to prepare. The study is basic science but could guide preventive approaches to vector-borne neuroinflammation, and Rice suggested early priming with an adjuvant or an interferon-based therapy similar to treatments used for chronic hepatitis C. The work received partial support from the Stavros Niarchos Foundation Institute for Global Infectious Disease Research at Rockefeller.
Difficult words
- interferon — protein signal that helps fight viral infectioninterferon-stimulated, interferon-based
- antiviral gene — gene that makes proteins to stop virusesinterferon-stimulated antiviral genes
- pathogen-associated molecular pattern — molecule part of a germ that triggers immunitypathogen-associated molecular patterns
- poly(I:C) — synthetic molecule used to mimic viral RNA
- transcriptomic program — pattern of gene activity in a celltranscriptomic programs
- microvascular endothelial cell — cell that lines small blood vesselsmicrovascular endothelial cells
- blood-brain barrier — cell layer that protects the brain from blood
- microglia — immune cells living inside the brain
- adjuvant — substance that increases an immune response
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Discussion questions
- Would you support preventive treatments that prime the immune system before travel to areas with vector-borne viruses? Why or why not?
- How could protecting or strengthening the blood-brain barrier help reduce brain infections? Give one or two reasons.
- What concerns or benefits might people have about treatments that use adjuvants or interferon-based therapy to prevent infections?
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