An in vitro investigation of core-like-particle assembly in Semliki Forest Virus

Alphaviruses are a geographically diverse genus spread by arthropod vectors such as mosquitos. They cause a wide range of rheumatic diseases such as arthritis and rheumatic arthritis and are a leading cause of encephalitis in both animals and humans. With epidemics arising each year and their dangerous zoonotic potential, alphaviruses are potential pandemic threats. There remains, as of 2023, no commercially available specific or direct acting therapeutic drugs to treat any alphavirus infection. A contributing factor to their absence is the lack of molecular understanding involved in high fidelity nucleocapsid assembly. This is a key stage within the viral lifecycle which was previously posited to be underpinned solely by electrostatic interactions between RNA and the coat protein. It has been demonstrated using other single-stranded, positive-sense RNA viruses- that efficient, high fidelity capsid assembly in vitro is regulated using the packaging-signal mediated mechanism. This reveals additional coding complexity within the genomic RNA and shows how sequence-specific interactions across the genome act cooperatively to mediate capsid assembly in vitro.