# Defining the impact of complement inhibition by tick saliva in tick-borne virus evolution and adaptive immune responses in murine models of infection

> **NIH NIH F31** · SAINT LOUIS UNIVERSITY · 2022 · $13,504

## Abstract

Disease caused by tick-borne viruses (TBVs) has been increasing in incidence in the past decade, with few
approved vaccines or therapeutics. Among these, the tick-borne flavivirus Powassan virus (POWV) is an RNA
virus which frequently causes neuroinvasive disease in humans and transmitted by Ixodes ticks. These and other
ticks are equipped with a unique store of salivary proteins that create an immunosuppressive environment
enabling long-term attachment to a host during a bloodmeal. One aspect of host-TBV interactions that is not well
understood is how the viral pathogens replicating in this niche may be afforded an advantage. This saliva
activated transmission (SAT) is known to occur with POWV infection, but the underlying mechanisms behind it
remain to be elucidated. This research proposed in this application will dissect how one important aspect of SGE
immunosuppression—complement inhibition—impacts the development of the adaptive immune response in
vaccinated and unvaccinated murine hosts, and how virus replication and subsequent dissemination to
secondary sites of replication can drive TBV disease.
In addition to existing expertise in TBVs and emerging infectious disease, our group has characterized the
kinetics of viral replication and the development of POWV-specific B and T cell responses in murine models of
infection. Furthermore, in conjunction with our collaborators, we have developed a virus-like particle (VLP) based
vaccination strategy capable of protecting against lethal POWV challenge. How complement inhibition impacts
the development of POWV-specific B and T cell responses in vaccinated and unvaccinated murine hosts is the
subject of Aim 1. Aim 2 focuses on quantifying the impact of complement inhibition on neuropathological disease
and virus evolution to drive disease in the murine host.
The fellowship training plan described in this proposal is designed to address important gaps in the applicant’s
training prior to completion of her doctoral dissertation defense. These gaps will primarily be addressed by: 1)
advancing the applicants repertoire of virology and immunology tools and high-impact publications, 2) allowing
the applicant to acquire a new skillset analyzing next generation sequencing data, 3) encouraging the applicant’s
attendance at in-person meetings for purposes of networking and seeking a suitable postdoctoral mentor. The
research and training goals set forth in this proposal will be accomplished in the environment of the sponsor and
co-sponsors at Saint Louis University and Colorado State University in a highly collaborative and trainee focused
setting.

## Key facts

- **NIH application ID:** 10535945
- **Project number:** 1F31AI172229-01
- **Recipient organization:** SAINT LOUIS UNIVERSITY
- **Principal Investigator:** Emily Taylor Stone
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $13,504
- **Award type:** 1
- **Project period:** 2023-01-01 → 2023-04-01

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10535945

## Citation

> US National Institutes of Health, RePORTER application 10535945, Defining the impact of complement inhibition by tick saliva in tick-borne virus evolution and adaptive immune responses in murine models of infection (1F31AI172229-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10535945. Licensed CC0.

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