Interaction of SARS-CoV-2 Nucleocapsid Protein and Human RNA Helicases DDX1 and DDX3X Modulates Their Activities on Double-Stranded RNA

• Published in: International journal of molecular sciences Vol. 24; no. 6; p. 5784
• Main Authors: Lodola, Camilla, Secchi, Massimiliano, Sinigiani, Virginia, De Palma, Antonella, Rossi, Rossana, Perico, Davide, Mauri, Pier Luigi, Maga, Giovanni
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01-03-2023; MDPI
• Subjects: Cells; Coronaviruses; COVID-19; DDX1; DDX3X; dead-box RNA helicase; DEAD-box RNA Helicases - genetics; Discriminant analysis; DNA helicase; Double-stranded RNA; Ectopic expression; Genetic transcription; Genomes; Genomics; Health aspects; Humans; Innate immunity; International economic relations; Kinases; Metabolism; nucleocapsid; Nucleocapsid Proteins; Nucleocapsids; Peptides; Protein expression; Proteins; Proteomes; RNA; RNA binding; RNA helicase; RNA Helicases; RNA, Double-Stranded; SARS-CoV-2; Scientific equipment and supplies industry; Severe acute respiratory syndrome coronavirus 2; Vaccines; United States; Sweden; Germany; nucleocapsid; SARS-CoV-2; DDX3X; DDX1; RNA binding; dead-box RNA helicase
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24065784

The nucleocapsid protein Np of SARS-CoV-2 is involved in the replication, transcription, and packaging of the viral genome, but it also plays a role in the modulation of the host cell innate immunity and inflammation response. Ectopic expression of Np alone was able to induce significant changes in the proteome of human cells. The cellular RNA helicase DDX1 was among the proteins whose levels were increased by Np expression. DDX1 and its related helicase DDX3X were found to physically interact with Np and to increase 2- to 4-fold its affinity for double-stranded RNA in a helicase-independent manner. Conversely, Np inhibited the RNA helicase activity of both proteins. These functional interactions among Np and DDX1 and DDX3X highlight novel possible roles played by these host RNA helicases in the viral life cycle.