An Evolutionary Insertion in the Mxra8 Receptor-Binding Site Confers Resistance to Alphavirus Infection and Pathogenesis.


Alphaviruses are emerging, mosquito-transmitted RNA viruses with poorly understood cellular tropism and species selectivity. Mxra8 is a receptor for multiple alphaviruses including chikungunya virus (CHIKV). We discovered that while expression of mouse, rat, chimpanzee, dog, horse, goat, sheep, and human Mxra8 enables alphavirus infection in cell culture, cattle Mxra8 does not. Cattle Mxra8 encodes a 15-amino acid insertion in its ectodomain that prevents Mxra8 binding to CHIKV. Identical insertions are present in zebu, yak, and the extinct auroch. As other Bovinae lineages contain related Mxra8 sequences, this insertion likely occurred at least 5 million years ago. Removing the Mxra8 insertion in Bovinae enhances alphavirus binding and infection, while introducing the insertion into mouse Mxra8 blocks CHIKV binding, prevents infection by multiple alphaviruses in cells, and mitigates CHIKV-induced pathogenesis in mice. Our studies on how this insertion provides resistance to CHIKV infection could facilitate countermeasures that disrupt Mxra8 interactions with alphaviruses.





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Publication Info

Kim, Arthur S, Ofer Zimmerman, Julie M Fox, Christopher A Nelson, Katherine Basore, Rong Zhang, Lorellin Durnell, Chandni Desai, et al. (2020). An Evolutionary Insertion in the Mxra8 Receptor-Binding Site Confers Resistance to Alphavirus Infection and Pathogenesis. Cell host & microbe, 27(3). pp. 428–440.e9. 10.1016/j.chom.2020.01.008 Retrieved from

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Carolyn Coyne

George Barth Geller Distinguished Professor of Immunology

We study the pathways by which microorganisms cross cellular barriers and the mechanisms by which these barriers restrict microbial infections. Our studies primarily focus on the epithelium that lines the gastrointestinal tract and on placental trophoblasts, the cells that comprise a key cellular barrier of the human placenta. Our work is highly multidisciplinary and encompasses aspects of cell biology, immunology, and microbiology. Our long-term goals are to identify pathogen- and host-specific therapeutic targets to prevent or treat microbial infections and ultimately to alleviate the morbidity and mortality caused by these infections.

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