# The role of antiviral programs in bacterial sepsis

> **NIH NIH R01** · INDIANA UNIVERSITY INDIANAPOLIS · 2021 · $401,016

## Abstract

Project Summary/Abstract
Sepsis is the most common cause of acute kidney injury in the intensive care unit and is coupled with very high
mortality. It is a highly dynamic pathological state in which a wide array of pro- and anti-inflammatory pathways
are aberrantly activated, resulting in a complex syndrome that evolves rapidly over hours. Therefore,
determining the timeline of sepsis and developing timeline-specific therapies are essential for successful
interventions. Recently, we examined temporal changes in the translatome of the kidney in animal models of
bacterial sepsis. We showed that 1) initial outburst of inflammation is accompanied by significant increases in
RNA transcription and translation, 2) the initial inflammatory phase is followed by activation of antiviral
programs, and 3) the activation of antiviral programs leads to translation shutdown—a hallmark of late phase
sepsis. Crucially missing from this recent work is the nature and source of the antiviral program activators in
the absence of an actual viral infection. We hypothesize that induction of the initial inflammatory cascades
results in a state of self-RNA overburden, which provokes a milieu resembling that of a viral infection. In this
proposal, we will investigate the role of endogenous RNA stress as the determinant of antiviral program
activation and resultant sepsis-induced organ failure. This work will provide an important framework for
understanding the link between the early phase inflammation and late phase total organ shutdown, and could
lead to novel diagnostic and therapeutic applications in sepsis-induced kidney failure.

## Key facts

- **NIH application ID:** 10269017
- **Project number:** 5R01AI148282-02
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Takashi Hato
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $401,016
- **Award type:** 5
- **Project period:** 2020-09-23 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10269017

## Citation

> US National Institutes of Health, RePORTER application 10269017, The role of antiviral programs in bacterial sepsis (5R01AI148282-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10269017. Licensed CC0.

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