# Molecular mechanisms governing the regulation of innate antiviral immunity by the SRMS kinase

> **NIH NIH R21** · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · 2020 · $207,187

## Abstract

The induction of type 1 interferon (IFN) antiviral response via the cytoplasmic, retinoic acid-inducible gene-I
(RIG-I)-like receptors (RLRs, RIG-I and MDA5) is a hallmark of the early host intrinsic immune responses to
viral infections in a majority of cell types. It confers immediate antiviral restriction and orchestrates the
development of subsequent adaptive immunity. This process is tightly regulated to ensure mounting timely
defense to viral insults while limiting harmful, excessive inflammatory responses. Elucidating the regulatory
mechanisms of RLR-mediated antiviral signaling not only helps understand host protective responses against
invading viruses and pathogenesis of viral infectious diseases, but also may provide crucial clues that aid the
design of safe and effective antiviral strategies. Autophagy is a homeostatic cellular process in which
cytoplasmic materials, including macromolecules, organelles, and sometimes invading pathogens, are
sequestered and delivered to lysosome for degradation. Recent evidence has suggested roles for autophagy
or autophagy-related proteins in orchestrating immunity and host responses to microbial infections, but current
knowledge on cellular kinases that regulate both autophagy and innate antiviral defense falls short. In
preliminary studies we have identified SRMS (Src-related kinase lacking C-terminal regulatory tyrosine and N-
terminal myristylation sites), a poorly characterized non-receptor tyrosine kinase, as a novel inhibitor of
autophagy and a molecule pivotal for virus-induced IFN response via the RLR pathway. However, the
underlying mechanisms are elusive. We hypothesize that SRMS is a novel player in innate antiviral defense
by facilitating RLR-dependent signaling and/or through regulating the autophagy pathway. Two specific
aims are proposed to test this hypothesis. In Aim 1, we will investigate the molecular determinants and
mechanism that govern the contribution of SRMS to the RLR signaling pathway leading to IFN-regulatory
factor-3 (IRF3) activation. In Aim 2, we will define the the domain(s) and residue(s) of SRMS important for
interaction with, phosphorylation of Beclin1 and autophagy restriction and determine the relationship between
SRMS-mediated autophagy regulation and its effect on RLR-dependent innate antiviral responses.
Completion of these studies will yield key insights into the novel role of SRMS in innate antiviral immunity, and
may lead to identification of new targets/pathways that can be harnessed for developing broad-spectrum
antiviral interventions for viral infectious diseases.

## Key facts

- **NIH application ID:** 9822179
- **Project number:** 5R21AI142044-02
- **Recipient organization:** UNIVERSITY OF TENNESSEE HEALTH SCI CTR
- **Principal Investigator:** KUI LI
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $207,187
- **Award type:** 5
- **Project period:** 2018-11-13 → 2022-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9822179

## Citation

> US National Institutes of Health, RePORTER application 9822179, Molecular mechanisms governing the regulation of innate antiviral immunity by the SRMS kinase (5R21AI142044-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9822179. Licensed CC0.

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