Characterization of SLA RNA promoter from dengue virus and its interaction with the viral non-structural NS5 protein - Archive ouverte HAL
Article Dans Une Revue Biochimie Année : 2024

Characterization of SLA RNA promoter from dengue virus and its interaction with the viral non-structural NS5 protein

Karl Brillet
Marta Janczuk-Richter
  • Fonction : Auteur
Amanda Poon
  • Fonction : Auteur
Joanne Laukart-Bradley
  • Fonction : Auteur
Eric Ennifar
  • Fonction : Auteur
  • PersonId : 1104727
Isabelle Lebars

Résumé

The Dengue virus (DENV) is the most significant arthropod-borne viral pathogen in humans with 400 million infections annually. DENV comprises four distinct serotypes (DENV-1 to -4) which complicates vaccine development. Any of the four serotypes can cause clinical illness but with distinctive infection dynamics. Variations in sequences identified within the four genomes induce structural differences in crucial RNA motifs that were suggested to be correlated to the degree of pathogenicity among DENV-1 to -4. In particular, the RNA Stem-loop A (SLA) at the 5'-end of the genome, acts as a key regulator of the viral replication cycle by interacting with the viral NS5 polymerase to initiate the minus-strand viral RNA synthesis and later to methylate and cap the synthesized RNA. The molecular details of this interaction remain not fully described. Here, we report the solution secondary structures of SLA from DENV-1 to -4. Our results highlight that the four SLA exhibit structural and dynamic differences. Secondly, to determine whether SLA RNA contains serotype-specific determinants for the recognition by the viral NS5 protein, we investigated interactions between SLA from DENV -1 to -4 and DENV2 NS5 using combined biophysical approaches. Our results show that NS5 from DENV2 is able to bind SLA from other serotypes, but that other viral or host factors may be necessary to stabilize the complex and promote the catalytically active state of the NS5. By contrast, we show that a serotype-specific binding is driven by specific interactions involving conformational changes within the SLA RNA.
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Dates et versions

hal-04646998 , version 1 (09-10-2024)

Identifiants

Citer

Karl Brillet, Marta Janczuk-Richter, Amanda Poon, Joanne Laukart-Bradley, Eric Ennifar, et al.. Characterization of SLA RNA promoter from dengue virus and its interaction with the viral non-structural NS5 protein. Biochimie, 2024, 222, pp.87-100. ⟨10.1016/j.biochi.2024.02.005⟩. ⟨hal-04646998⟩

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