Mxra8 is a receptor for multiple arthritogenic alphaviruses

Area of Science:

• Virology
• Immunology
• Molecular Biology

Background:

• Arthritogenic alphaviruses cause significant musculoskeletal disease in humans.
• Host factors mediating alphavirus entry into cells are not well understood.

Purpose of the Study:

• To identify host factors essential for arthritogenic alphavirus cell entry.
• To evaluate Mxra8 as a potential therapeutic target against alphavirus infections.

Main Methods:

• Genome-wide CRISPR-Cas9 screening to identify host entry factors.
• Gene editing (knockout and ectopic expression) of Mxra8 in mammalian cells.
• In vitro binding assays and infection blocking studies using Mxra8-Fc fusion proteins and monoclonal antibodies.
• In vivo studies in mouse models to assess therapeutic efficacy.

Main Results:

• Mxra8 was identified as a critical mediator for the entry of multiple arthritogenic alphaviruses.
• Mxra8 directly binds to viral particles and facilitates virus attachment and internalization.
• Blocking Mxra8 function significantly reduced viral infection in various human cell types and in mice.
• Therapeutic intervention targeting Mxra8 decreased viral load and attenuated disease symptoms in vivo.

Conclusions:

• Mxra8 is a crucial host cell receptor for arthritogenic alphaviruses.
• Targeting Mxra8 presents a promising therapeutic strategy to combat infections caused by chikungunya, Ross River, Mayaro, and O'nyong nyong viruses.