Live-attenuated flavivirus vaccines confer long-term protection against disease, but the design of attenuated flaviviruses does not follow a general approach. The non-coding, subgenomic flavivirus RNA (sfRNA) is produced by all flaviviruses and is an essential factor in viral pathogenesis and transmission. We argue that modulating sfRNA expression is a promising, universal strategy to finetune flavivirus attenuation for developing effective flavivirus vaccines of the future.
Keywords: Japanese encephalitis virus; West Nile virus; Zika virus; flavivirus; live-attenurated; noncoding RNA; sfRNA; tick-borne encephalitis virus; vaccines.