# Elucidating How Tri-phosphatase DUSP11 Controls HCV Infection and Hepatocyte Inflammation

> **NIH NIH R01** · UNIVERSITY OF TEXAS AT AUSTIN · 2021 · $449,504

## Abstract

PROJECT SUMMARY
Both the clearance of hepatitis C virus (HCV) and its disease manifestations are associated with the
inflammatory response. Yet, large gaps in knowledge exist about the factors that initiate inflammation and
control HCV replication. There is an urgent need to fill these gaps because determining the mechanisms that
control HCV infection and associated inflammation is imperative for understanding HCV-associated disease.
The long-term goal of this collaborative team is to understand the mechanisms of HCV innate control and
pathogenesis. Consistent with this goal, the overall objective in this proposal is to determine how the RNA
triphosphatase DUSP11 is associated with control of both HCV infection and pro-inflammatory RNA
transcripts. The central hypothesis is that DUSP11 promotes turnover of pro-inflammatory host and viral
triphosphorylated transcripts, thereby reducing HCV replication and RNA-associated inflammation. The
rationale for this proposed research is that, once it is known how DUSP11 functions in control of virus
replication and host pro-inflammatory transcripts, this will advance understanding of the innate defenses
against HCV, imperative for guiding future rational vaccine designs and for developing therapeutic strategies to
address HCV-induced liver pathogenesis. Testing the central hypothesis and completing the objectives
outlined in this proposal will be accomplished via the following two specific aims: 1) Determine the anti-HCV
mechanism of DUSP11 in liver cells, and 2) Determine the function of DUSP11 in controlling inflammation
associated with pro-inflammatory viral and host RNAs. Under the first aim, knockout approaches combined
with cell, molecular and biochemical experiments will reveal how DUSP11 and its partners inhibit HCV virus
infection and how the virus counters this restriction by binding the cellular microRNA, miR-122. Under the
second aim, specialized high-throughput tri-phosphate-specific RNA sequencing technology combined with
knockout mice will determine how DUSP11 controls inflammation associated with viral and host pro-
inflammatory RNAs in cultured cells and in vivo. The contribution here is expected to be a detailed
understanding of the mechanisms of how DUSP11 restricts HCV replication and modulates pro-inflammatory
activities of viral and host RNAs during infection. These contributions will be significant because they are
expected to have broad translational importance for understanding the activity and possible viral resistance
mechanisms of current phase II anti-miR-122 HCV drugs as well as informing the interface of innate and
adaptive immune response – key for rational vaccine design. The research proposed in this application is
innovative because it represents a new and substantive departure from the status quo by focusing on
DUSP11, a single protein that promotes both restriction of HCV and control of inflammation triggered by host
and viral RNAs. The results from this proposed work wi...

## Key facts

- **NIH application ID:** 10199990
- **Project number:** 5R01AI134980-04
- **Recipient organization:** UNIVERSITY OF TEXAS AT AUSTIN
- **Principal Investigator:** Glenn C Randall
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $449,504
- **Award type:** 5
- **Project period:** 2018-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10199990

## Citation

> US National Institutes of Health, RePORTER application 10199990, Elucidating How Tri-phosphatase DUSP11 Controls HCV Infection and Hepatocyte Inflammation (5R01AI134980-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10199990. Licensed CC0.

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