Innovating Works

MOVIRNA

Financiado
Non-canonical modification of viral RNA
Viruses cause significant disease, exemplified by the COVID-19 pandemic. Most studies of virus-host interactions focused on proteins, however, RNA holds great promise for basic and therapeutic exploration. Viruses evolved elaborat... Viruses cause significant disease, exemplified by the COVID-19 pandemic. Most studies of virus-host interactions focused on proteins, however, RNA holds great promise for basic and therapeutic exploration. Viruses evolved elaborate strategies for RNA protection, including 5’ capping and internal modification. The goal of this proposal is to discover and characterize viral RNA modifications installed by viral enzymes, including their role in innate immune evasion. This could uncover novel RNA-based mechanisms of viral replication and host modulation and lead to therapeutic targets. Many viruses encode methyltransferases (MTases) for canonical RNA 5’ capping. Curiously, no cap was identified for hepatitis C virus (HCV), an important human pathogen. We recently found that the cellular metabolite, flavin adenine dinucleotide (FAD), is used as noncanonical initiating nucleotide by the HCV polymerase at high frequency resulting in a 5’FAD cap on HCV RNA. This is the first description of a virus using this cap type for protecting its RNA and, remarkably, the first robust description of FAD capping across any kingdom of life. In Aim 1, we will investigate the functional role of the HCV 5’FAD cap, including viral evasion of innate immune sensing and RNA stability. We will also explore the evolutionary conservation of metabolite capping across RNA viruses and explore its potential as antiviral target. Viral MTases further perform 2’-O-methylation (2’OMe) of internal RNA residues, a modification that also may protect from innate recognition. In Aim 2, the extent of 2’OMe on viral RNA will be mapped and the individual contribution of 5’ and internal modification to innate immune evasion will be dissected. In aggregate, these aims will uncover how viral enzymes modify the termini and internal viral RNA residues and associated evasion of innate immunity. The outcome could reshape understanding of viral RNA biology, open novel research directions and lead to antiviral targets. ver más
30/06/2029
UCPH
2M€
Perfil tecnológico estimado
Duración del proyecto: 66 meses Fecha Inicio: 2023-12-12
Fecha Fin: 2029-06-30

Línea de financiación: concedida

El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2023-12-12
Línea de financiación objetivo El proyecto se financió a través de la siguiente ayuda:
ERC-2023-COG: ERC CONSOLIDATOR GRANTS
Cerrada hace 1 año
Presupuesto El presupuesto total del proyecto asciende a 2M€
Líder del proyecto
KOBENHAVNS UNIVERSITET No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico TRL 4-5