Attenuation of encephalitogenic alphavirus and uses thereof

摘要

The present invention is drawn to generating attenuated and less cytopathic forms of New World alphaviruses that can be used in immunogenic compositions as vaccines against both Old and New World alphaviruses. In this regard, the present invention discloses that the N-terminal, ˜35-aa-long peptide of VEEV, EEEV and, most likely, of WEEV capsid proteins plays the most critical role in the downregulation of cellular transcription and development of cytopathic effect. The identified, VEEV-specific peptide, C_VEE30-68, includes two domains with distinguished functions. The integrity of both domains determines not only the intracellular distribution of C_VEE, but is also essential for direct capsid function in the inhibition of transcription. The replacement of the N-terminal fragment of C_VEE by its SINV-specific counterpart in VEEV TC-83 genome does not affect virus replication in vitro, but makes it less cytopathic and more attenuated in vivo.