# Deconvolution of pro- and anti-viral responses to Dengue virus and Zika Virus infections

> **NIH NIH K08** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2022 · $203,796

## Abstract

Project Summary/Abstract:
The interferon-regulatory factor (IRFs) family of transcription factors (TFs) are central regulators of anti-viral
responses. They translate signals from pathogen recognition receptors into complex transcriptional
responses that are essential for viral control. Targeted genetic deletion of IRF TFs in mice increase
susceptibility to viruses, which in turn have evolved mechanism to deactivate IRF signaling leading to
increased virulence. Despite their importance, we still do not understand how IRFs coordinate the control of
transcription to protect us from viruses. IRF TFs share structural homology in their DNA binding domains and
bind highly similar DNA motifs. Yet, they regulate non-redundant antiviral transcriptional programs. The
overall objective of this proposal is to determine how anti-viral IRF TFs act on a gene specific and genome
wide scale to control anti-viral responses. The experiments in specific aim 1 will investigate why DENV, and
not ZIKV, appears to stimulate IRF-1 and IFNγ responses. Additional studies will test if the lack of IFNγ
response can help explain ZIKV neuropathology. Studies in specific Aim 2 will identify genome-wide networks
of IRF gene activation and transcriptional signatures during DENV and ZIKV infections. Comparisons of
responses in infected and uninfected neighboring cells will identify viral subversion of host cell signaling.
Additionally, comparing responses in DENV and ZIKV infected cells will identify viral specific activation of
IRF-dependent responses. Lastly, integration of genome-wide signal dependent and lineage determining TF
binding and genomic features of active enhancers will help establish basic principals governing how IRFs
cooperate with each other and other TFs to establish functional enhancers and control gene expression.
Together this proposal will identify basic principals governing IRF regulation of viral responses and identify
differences in viral specific IRF responses that may explain disease pathogenesis and advance treatments for
these currently untreatable infections.

## Key facts

- **NIH application ID:** 10319989
- **Project number:** 5K08AI130381-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Aaron F. Carlin
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $203,796
- **Award type:** 5
- **Project period:** 2019-01-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10319989

## Citation

> US National Institutes of Health, RePORTER application 10319989, Deconvolution of pro- and anti-viral responses to Dengue virus and Zika Virus infections (5K08AI130381-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10319989. Licensed CC0.

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