# Structure-Function Analysis of Mxra8 Interaction with Alphaviruses.

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2021 · $646,002

## Abstract

Project Summary/ Abstract
Alphaviruses are mosquito-transmitted, positive-strand enveloped RNA viruses of the Togaviridae family that
cause global disease in humans. At present, no antiviral agents or licensed vaccines exist for the treatment or
prevention of any alphavirus infections. We recently used a genome-wide CRISPR/Cas9-based screen to identify
the cell surface molecule Mxra8 as a novel entry receptor for multiple emerging alphaviruses that cause arthritis
and musculoskeletal disease including chikungunya (CHIKV), Ross River (RRV), Mayaro, (MAYV), and O'nyong
nyong (ONNV) viruses. Gene editing of mouse Mxra8 or human MXRA8 resulted in reduced alphavirus infection
of cells, and reciprocally, ectopic expression resulted in increased infection. Mxra8 bound directly to CHIKV
particles and enhanced virus attachment and internalization into cells. We hypothesize that engagement of
Mxra8 by different alphaviruses will explain how infection, tissue targeting, and disease pathogenesis occurs.
The primary goals of this collaborative proposal between the Diamond, Fremont, and Smit laboratories are
to define the precise mechanism(s) by which Mxra8 facilitates alphavirus entry into cells, to gain high-
resolution structural insight as to how Mxra8 engages the alphavirus virion, and to determine the detailed
role of Mxra8 in the pathogenesis of acute and chronic infection of multiple arthritogenic alphaviruses in
vivo using novel murine models. The experiments in this proposal will define fundamental aspects of alphavirus
biology that enhance our understanding of infection and cell tropism. This information may facilitate the
development of small molecules or biologicals that disrupt Mxra8 interaction with alphavirus spike proteins, which
could form the basis of future therapeutics that ameliorate disease of multiple emerging alphaviruses.

## Key facts

- **NIH application ID:** 10169235
- **Project number:** 5R01AI143673-03
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Michael S Diamond
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $646,002
- **Award type:** 5
- **Project period:** 2019-06-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10169235

## Citation

> US National Institutes of Health, RePORTER application 10169235, Structure-Function Analysis of Mxra8 Interaction with Alphaviruses. (5R01AI143673-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10169235. Licensed CC0.

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