# Gut Microbiota Modulation of Chikungunya Virus Infection and Pathogenesis

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2021 · $624,846

## Abstract

PROJECT SUMMARY
Chikungunya virus (CHIKV) is a mosquito-transmitted, positive-strand enveloped alphavirus that causes global
disease in humans. At present, no antiviral agents or licensed vaccines exist for the treatment or prevention of
any alphavirus infections. While age, immune status, and pre-existing chronic illness are associated with
increased risk of severe CHIKV infection, the role of acquired factors in disease progression is poorly understood.
Our preliminary data suggests that the microbiota regulates CHIKV infection, dissemination, and musculoskeletal
inflammation and disease through a previously undefined axis by which signals from gut bacteria and bile acids
instruct innate immune cell responses to control CHIKV infection of monocytes in circulation and monocyte
migration to affected joint tissues. We hypothesize that specific gut bacteria and their microbial constituents
modulate CHIKV pathogenesis by regulating antiviral type I IFN and inflammatory responses in pDCs and
monocytes. In the absence of these microbial signals, CHIKV disseminates widely, and arthritis ensues after
joint infiltration by immune cells. This proposal combines investigators with expertise in alphavirus pathogenesis
and immunity (Diamond) and the study of the gut microbiota in disease (Handley, Stappenbeck, and Fischbach).
Using a suite of transgenic mice and microbiome reconstitution experiments paired with detailed virological and
immunological analyses, we will address the following key questions: (a) which immune cells coordinate the
rapid systemic IFN response following CHIKV infection (e.g., pDCs) (b) what immune cues limit viral infection in
circulating immune cells (e.g., monocytes)? (c) how does the gut microbiota regulate pDC IFN production and
trafficking of circulating immune cells? and (d) which constituents (e.g., metabolites) of the microbiota regulate
antiviral and inflammatory responses? Through these detailed mechanistic studies, we expect to link the
microbe-derived constituents of specific commensal bacteria with innate antiviral responses that modulate
alphavirus infection, dissemination, joint disease, and possibly transmission. Beyond enhancing our
understanding of acquired determinants of alphavirus pathogenesis, the findings of this proposal could inform
more generally our understanding of how the gut microbiota shapes innate immune responses to limit infection
and pathogenesis of other viruses.

## Key facts

- **NIH application ID:** 10123929
- **Project number:** 1R01AI152484-01A1
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Michael S Diamond
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $624,846
- **Award type:** 1
- **Project period:** 2021-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10123929

## Citation

> US National Institutes of Health, RePORTER application 10123929, Gut Microbiota Modulation of Chikungunya Virus Infection and Pathogenesis (1R01AI152484-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10123929. Licensed CC0.

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