# Interferon-mediated control of neuropathogenic Flaviviruses

> **NIH NIH K08** · UT SOUTHWESTERN MEDICAL CENTER · 2020 · $148,770

## Abstract

Title: Interferon-Mediated Control of Neuropathogenic Flaviviruses
Abstract:
The primary research goals of this Mentored Clinical Scientist Research Career Development Award proposal
are to study mechanisms by which antiviral interferons suppress neuropathogenic Flaviviruses. Flaviviruses,
including Zika virus (ZIKV) and West Nile virus (WNV), can cause severe neurological complications, including
brain disruption sequence and encephalitis. These manifestations are the net result of both virus-induced effects
and host immune responses. The type I interferon (IFN) response establishes a cellular antiviral state through
the induction of hundreds of IFN-stimulated genes (ISGs), many of which have direct antiviral effects. Through
a cell-based screen to identify novel antiviral ISGs, the candidate uncovered C19orf66 as a potent inhibitor of
multiple RNA viruses, including WNV, ZIKV, and Venezuelan equine encephalitis virus (VEEV). The candidate
has shown that C19orf66 is required for an optimal IFN response and targets the viral life cycle at the stage of
genome replication. Additionally, C19orf66 is basally expressed in primary human neural progenitor cells (hNPs),
a useful model to study Zika virus-host interaction. Here, the candidate proposes to further characterize the
mechanism of C19orf66 inhibition of Flaviviruses. A combination of molecular virological, cell biological, and
biochemical approaches will be used to study: 1) the precise viral life cycle step inhibited by C19orf66, 2) the
contribution of C19orf66 to antiviral immunity in hNP cell culture models and 3) the in vivo relevance in a mouse
model of ZIKV infection. This research plan, complemented by a comprehensive career development plan that
capitalizes on the candidate’s strong clinical interest in central nervous system infections, will lead to an
independent research career laid on the foundation of strong education and sound technical skills. The research
component of this award will be conducted in the laboratory of Dr. John Schoggins at UT Southwestern, who
has significant expertise in basic virology and innate immunity, with additional oversight by co-mentor, Dr. Beth
Levine, an expert in virus-host interactions with a strong history of successful mentorship. Critical to the
candidate’s career development are attendance and presentations at professional conferences, regular
meetings with her advisory committee, courses in fundamentals of neuroscience and immunology, mentorship
and career development, research ethics, and hands-on training in the neuroscience lab of Dr. Genevieve
Konopka. In summary, this training plan will satisfy the candidate’s short-term goals to strengthen her
neuroscience and immunology fund of knowledge and expand her experience in basic science, providing for her
long-term goal of independent research in the innate immune control of neuropathogenic Flaviviruses.

## Key facts

- **NIH application ID:** 9869843
- **Project number:** 5K08AI132751-02
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Natasha Wyndham Hanners
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $148,770
- **Award type:** 5
- **Project period:** 2019-02-12 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9869843

## Citation

> US National Institutes of Health, RePORTER application 9869843, Interferon-mediated control of neuropathogenic Flaviviruses (5K08AI132751-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9869843. Licensed CC0.

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