# Viral and Host Determinants of Chikungunya Virus Dissemination

> **NIH NIH F32** · UNIVERSITY OF COLORADO DENVER · 2020 · $65,310

## Abstract

PROJECT SUMMARY
Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes epidemics of severe
rheumatologic disease. The impact of CHIKV disease extends globally, with recent outbreaks occurring in
Asia, Europe and the Americas. Up to 50% of patients report persistent rheumatologic symptoms, with
incapacitating arthralgia lasting for months to years after infection. Chronic disease has been linked in humans
and animal models with persistent CHIKV infection. Despite this, the host-viral interactions that dictate viral
clearance or persistence are poorly defined. To identify adaptive mutations associated with chronic CHIKV
infection, the Morrison laboratory isolated CHIKV from the circulation of a chronically-infected Rag1-/- mouse.
This virus contained a mutation in the E2 glycoprotein (E2 K200R) that dramatically enhances viremia and viral
dissemination in WT mice, leading to more severe disease outcomes. Moreover, introduction of an E2 K200R
mutation into additional CHIKV strains or a closely related alphavirus, o'nyong nyong virus, also enhances
viremia, demonstrating this mutation evades a host response that is operative against multiple alphaviruses.
High viremia in humans and non-human primates infected with CHIKV has been associated with more severe
acute disease and an increased potential for chronic disease. Therefore, this mutant virus provides a valuable
tool to identify host and viral determinants of alphavirus dissemination and pathogenicity. The enhanced
dissemination mediated by CHIKV E2 K200R (CHIKVE2 K200R) is independent of type I IFN, demonstrating that
additional innate immune responses significantly contribute to CHIKV control. My preliminary data
demonstrates that WT CHIKV particles are rapidly cleared from the circulation following intravenous
inoculation, while CHIKVE2 K200R particles remain stably detectable. Depletion of phagocytic cells prevents
clearance of WT CHIKV from the circulation, but has no impact on the circulating levels of CHIKVE2 K200R.
These findings reveal a critical role for phagocytic cells in controlling WT CHIKV dissemination and suggest
that CHIKVE2 K200R evades clearance by phagocytic cells. My objective is to define the phagocytic cells that are
responsible for CHIKV clearance, and to define the viral determinants of clearance and escape. Based on my
preliminary data, I hypothesize that splenic red pulp macrophages efficiently capture WT CHIKV, and that
CHIKVE2 K200R evades this response by abrogating interactions with a conserved residue in the E1 glycoprotein,
resulting in structural alterations that facilitate evasion of phagocytic cells. In Aim 1, I will precisely define the
population of phagocytic cells that mediate CHIKV clearance from the circulation. In Aim 2, I will define viral
determinants that mediate CHIKV clearance by phagocytic cells or escape of this clearance mechanism. The
proposed research will significantly advance the field by defining new mechanisms of host co...

## Key facts

- **NIH application ID:** 9824449
- **Project number:** 5F32AI140567-02
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Kathryn Semmens Carpentier
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $65,310
- **Award type:** 5
- **Project period:** 2018-11-01 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9824449

## Citation

> US National Institutes of Health, RePORTER application 9824449, Viral and Host Determinants of Chikungunya Virus Dissemination (5F32AI140567-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9824449. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*