AI Article Synopsis
- Mxra8 is a receptor linked to several alphaviruses, including Chikungunya and others, and was studied to understand its function in disease development.
- Researchers created mutant mice with altered Mxra8 genes, leading to reduced viral infections and symptoms like foot swelling when infected with Chikungunya virus.
- The findings indicate that Mxra8 plays a significant role in how these viruses cause diseases, suggesting that targeting Mxra8 could help develop treatments for infections in humans.
Article Abstract
Mxra8 is a recently described receptor for multiple alphaviruses, including Chikungunya (CHIKV), Mayaro (MAYV), Ross River (RRV), and O'nyong nyong (ONNV) viruses. To determine its role in pathogenesis, we generated mice with mutant Mxra8 alleles: an 8-nucleotide deletion that produces a truncated, soluble form (Mxra8) and a 97-nucleotide deletion that abolishes Mxra8 expression (Mxra8). Mxra8 and Mxra8 fibroblasts show reduced CHIKV infection in culture, and Mxra8 and Mxra8 mice have decreased infection of musculoskeletal tissues with CHIKV, MAYV, RRV, or ONNV. Less foot swelling is observed in CHIKV-infected Mxra8 mutant mice, which correlated with fewer infiltrating neutrophils and cytokines. A recombinant E2-D71A CHIKV with diminished binding to Mxra8 is attenuated in vivo in wild-type mice. Ectopic Mxra8 expression is sufficient to enhance CHIKV infection and lethality in transgenic flies. These studies establish a role for Mxra8 in the pathogenesis of multiple alphaviruses and suggest that targeting this protein may mitigate disease in humans.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6745702 | PMC |
| http://dx.doi.org/10.1016/j.celrep.2019.07.105 | DOI Listing |
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