MXRA8 as a Gateway for Chikungunya Virus: From Pathogenesis, Cross-species Transmission to Novel Therapeutics

Abstract

Chikungunya virus (CHIKV), transmitted by Aedes aegypti and Aedes albopictus mosquitoes, is a growing global health concern. Human infection often manifests with high fever, rash, and debilitating pain and swelling in multiple joints. A pivotal discovery in the field was the identification of matrix remodeling-associated protein 8 (MXRA8) as a key host receptor that facilitates CHIKV cellular entry. MXRA8 is highly expressed in muscle, joint, and tendon tissues, which aligns with the viral primary target organs. MXRA8 knockout significantly inhibits viral infection, while soluble MXRA8-Fc fusion proteins or blocking antibodies can effectively prevent infection and alleviate diseases. CHIKV achieves cross-species transmission by leveraging the highly conserved nature of MXRA8 across different species. Although no specific antiviral drugs for CHIKV are currently approved, therapeutic strategies targeting MXRA8, such as decoy receptors and neutralizing antibodies, show considerable promise. When combined with mosquito control and vaccine development, these MXRA8-based approaches offer a hopeful outlook for controlling the spread of CHIKV.