CE11 - Caractérisation des structures et relations structure-fonction des macro-molécules biologiques

Investigation of the structure, biological roles and mechanisms of action of CHIKV macro-complexes made of non-structural proteins – CHIK-MaC

Submission summary

Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that has re-emerged in many parts of Africa, Asia and America causing large-scale epidemics in the last decades. CHIKV is increasingly recognized as an important public health problem, due to rapid spread of infection that characterizes epidemics, the spread of the virus and Aedes mosquito vector, and the lack of a cure or vaccine.
CHIKV encodes four so-called non-structural proteins (nsPs) that assemble and recruit host factors within specialized membrane organelles called spherules to form the viral replication complexes (RC) which are critical for viral genome amplification. To date, the 3D architecture and structural organization of the CHIKV RC remains enigmatic and represents a major challenge in this reseach area. In addition, emerging evidences showed that the CHIKV nsPs play poorly characterized but essential functions outside their role in building the RC. For instance, we showed that nsP1, the RNA capping enzyme, forms membrane associated rings outside RCs and we have evidence for nsP3 macrostructures at late stages of CHIK infection. Important questions raised by these studies are what are the functions of these macrostructures for the infection and pathogenesis.
CHIKVMaC aims to explore the structural biology if thee nsP-mediated macro complexes focusing on the nsP1 rings, the nsP3 macrostructures and the full RCs. This will allow to contextualize their enzymatic activities, host interactions and their interrelationships in a more realistic context. By knowing how these four proteins work together for carrying out infection, we will provide important information for the design of new antivirals to stop the expansion of Chikungunya and related alphavirus.

Project coordination

Juan Reguera (Université Aix-Marseille)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.


AFMB Université Aix-Marseille
GenCellDis Génomes, biologie cellulaire et thérapeutique

Help of the ANR 544,971 euros
Beginning and duration of the scientific project: December 2022 - 48 Months

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