Why the study?
Human noroviruses are the leading cause of severe childhood diarrhea worldwide, but little is known about their pathogenic mechanisms, and existing murine models in interferon-deficient mice feature systemic pathology and lethality that reduce translatability.
Does murine norovirus infection cause self-resolving diarrhea without systemic disease in wild-type neonatal mice?
Does murine norovirus infection cause self-resolving diarrhea without systemic disease in wild-type neonatal mice?
A novel small animal model using wild-type neonatal mice infected with murine norovirus mirrors key features of human norovirus disease.
Answers are grounded in this paper and cite their sources.
Establishes a wild-type neonatal mouse model of norovirus diarrhea; leaves open translation to human mechanisms or therapies.
Human noroviruses are the leading cause of severe childhood diarrhea worldwide yet we know very little about their pathogenic mechanisms. Murine noroviruses cause diarrhea in interferon-deficient adult mice but these hosts also develop systemic pathology and lethality, reducing confidence in the translatability of findings to human norovirus disease. Herein we report that a murine norovirus causes self-resolving diarrhea in the absence of systemic disease in wild-type neonatal mice, thus mirroring the key features of human norovirus disease and representing a robust norovirus small animal disease model. Intriguingly, lymphocytes are critical for controlling acute norovirus replication while simultaneously contributing to disease severity, likely reflecting their dual role as targets of viral infection and key components of the host response.
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Roth et al. (2020) studied this question.
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