Current therapies for human cytomegalovirus (HCMV) are associated with serious side effects and drug resistance. Now, Spiess et al. describe a novel fusion toxin protein (FTP)-based strategy to target HCMV on the basis of the viral expression of the internalizing G protein-coupled receptor, US28, which binds chemokines (particularly CX3CL1) as part of the immune-evasive function of the virus. They engineered a synthetic CX3CL1 variant displaying high affinity for US28 and greater specificity for US28 than does the natural CX3CL1 receptor, CX3CR1, and fused this with the cytotoxic domain of Pseudomonas exotoxin A. The resulting FTP prevented HCMV replication in cells and mice with greater potency than ganciclovir.
References
Spiess, K. et al. Rationally designed chemokine-based toxin targeting the viral G protein-coupled receptor US28 potently inhibits cytomegalovirus infection in vivo. Proc. Natl Acad. Sci. USA 112, 8427–8432 (2015)
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Crunkhorn, S. Fusion toxin protein inhibits CMV infection. Nat Rev Drug Discov 14, 528 (2015). https://doi.org/10.1038/nrd4700
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DOI: https://doi.org/10.1038/nrd4700
