Functional studies on the formation of Chikungunya virus replicase through the trans-complementation of defected replicase components

Abstract

Chikungunya virus has a positive-strand RNA genome and belongs to the Alphavirus genus. The viral replication complex includes four non-structural proteins (nsP1-4) which are needed for the virus replication. Several mutations in the non-structural region have been described which impair the formation and functioning of the replication complexes. The alphavirus replicase possesses trans activity which has enabled for the construction of trans-replication systems. These systems provide efficient tools for studying the replication of alphaviruses. The aim of this study was to explore the possibility of trans-complementing the impaired functions of CHIKV nsP1, nsP2 and nsP3 proteins by supplying a functional counterpart in trans. This thesis demonstrated that the inactivity of the CHIKV replicases can be, in some cases, trans-complemented.