Mxra8, also known as Matrix-remodeling-associated protein 8, is a transmembrane protein. It functions as an entry mediator for multiple arthritogenic alphaviruses, including chikungunya, Ross River, Mayaro and O'nyong nyong viruses [1]. It binds directly to chikungunya virus particles and enhances virus attachment and internalization into cells, playing a crucial role in alphavirus-related musculoskeletal diseases [1]. Genetic models, such as gene-edited mice, are valuable for studying its function.

Gene editing of mouse Mxra8 resulted in reduced levels of viral infection of cells. Mxra8 knockout (MXRA8-/-) mice generated on a C57BL/6J background showed abrogated disease signs and reduced viral replication, with lower viral load, diminished proinflammatory cytokines, and limited cell infiltrates in inflamed tissues when infected with Ross River virus (RRV) [1,2]. Mxra8Δ8/Δ8 and Mxra8Δ97/Δ97 mice also had decreased infection of musculoskeletal tissues with multiple alphaviruses like CHIKV, MAYV, RRV, or ONNV, and less foot swelling was observed in CHIKV-infected Mxra8 mutant mice, which correlated with fewer infiltrating neutrophils and cytokines [3].

In conclusion, Mxra8 is essential for alphavirus infection and pathogenesis. Studies using Mxra8 knockout mouse models have revealed its role in alphavirus-induced musculoskeletal inflammation, highlighting its importance in understanding and potentially mitigating alphavirus-related diseases.