Targeted entry of enveloped viruses: measles and herpes simplex virus I

We compare the receptor-based mechanisms that a small RNA virus and a larger DNA virus have evolved to drive the fusion of viral and cellular membranes. Both systems rely on tight control over triggering the concerted refolding of a trimeric fusion protein. While measles virus entry depends on a receptor-binding protein and a fusion protein only, the herpes simplex virus (HSV) is more complex and requires four viral proteins. Nevertheless, in both viruses a receptor-binding protein is required for triggering the membrane fusion process. Moreover, specificity domains can be appended to these receptor-binding proteins to target virus entry to cells expressing a designated receptor. We discuss how principles established with measles and HSV can be applied to targeting other enveloped viruses, and alternatively how retargeted envelopes can be fitted on foreign capsids.

► Targeting: addition of specificity domains to the receptor-binding protein ► Entry targeting of viral vectors improves efficacy of oncolytic and gene therapies ► Enveloped viruses measles and herpes simplex virus I have been successfully retargeted ► Envelope exchange for viruses with prohibitive entry constraints.