# Circadian control of enteric virus infection

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 2022 · $583,262

## Abstract

Project Summary/Abstract
Circadian rhythms are 24h oscillations in a variety of processes that are entrained by environmental cues
including light. Molecularly, this “clock” is driven by key transcription factors and feedback loops that generate
rhythmic expression of thousands of mammalian genes in a variety of tissues. Past work has revealed the
impact of circadian rhythms on metabolism and immunity. However, the impact of circadian rhythms on
infection, particularly enteric virus infection, is understudied. Preliminary experiments using the enteric virus
coxsackievirus B3 (CVB3) revealed a profound circadian effect on infection: Mice orally inoculated with CVB3
in the morning had viral titers 10-100 fold lower than mice inoculated in the evening. Inhibition of viral
replication in the morning correlated with increased expression of antiviral proteins at this time. Circadian
effects on CVB3 infection were lost in mice lacking certain proteins involved in interferon-mediated antiviral
responses, suggesting a possible link between circadian transcriptional control and innate immune responses
in the intestine. Indeed, expression of an antiviral protein was lost in mice that lack activity of an important
clock transcription factor. Thus, CVB3 infection is under circadian control and rhythmic host interferon
responses contribute to these effects. However, several questions remain. In this work we will 1) examine
mechanisms by which clock transcription factors control expression of innate immune genes, 2) examine the
effect of clock transcription factors on infection with CVB3 and other enteric viruses, and 3) identify and
evaluate cell types in the intestine that contribute to circadian control of enteric virus infection. Answering
these questions will illuminate key, but unanticipated, aspects of intestinal biology that influence enteric virus
infection.

## Key facts

- **NIH application ID:** 10363721
- **Project number:** 5R01AI158351-02
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Julie K Pfeiffer
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $583,262
- **Award type:** 5
- **Project period:** 2021-03-03 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10363721

## Citation

> US National Institutes of Health, RePORTER application 10363721, Circadian control of enteric virus infection (5R01AI158351-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10363721. Licensed CC0.

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