RESUMO
Genome-wide approaches have significantly advanced our knowledge of the repertoire of RNA-binding proteins (RBPs) that associate with cellular polyadenylated mRNAs within eukaryotic cells. Recent studies focusing on the RBP interactomes of viral mRNAs, notably SARS-Cov-2, have revealed both similarities and differences between the RBP profiles of viral and cellular mRNAs. However, the RBPome of influenza virus mRNAs remains unexplored. Herein, we identify RBPs that associate with the viral mRNA encoding the nucleoprotein (NP) of an influenza A virus. Focusing on TDP-43, we show that it binds several influenza mRNAs beyond the NP-mRNA, and that its depletion results in lower levels of viral mRNAs and proteins within infected cells, and a decreased yield of infectious viral particles. We provide evidence that the viral polymerase recruits TDP-43 onto viral mRNAs through a direct interaction with the disordered C-terminal domain of TDP-43. Notably, other RBPs found to be associated with influenza virus mRNAs also interact with the viral polymerase, which points to a role of the polymerase in orchestrating the assembly of viral messenger ribonucleoproteins.
Assuntos
Proteínas de Ligação a DNA , Vírus da Influenza A , RNA Mensageiro , RNA Viral , Proteínas de Ligação a RNA , Replicação Viral , Humanos , Replicação Viral/genética , RNA Viral/metabolismo , RNA Viral/genética , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/genética , RNA Mensageiro/metabolismo , RNA Mensageiro/genética , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , Vírus da Influenza A/genética , Vírus da Influenza A/fisiologia , Vírus da Influenza A/metabolismo , Proteínas do Nucleocapsídeo/metabolismo , Proteínas do Nucleocapsídeo/genética , Células HEK293 , Proteínas do Core Viral/metabolismo , Proteínas do Core Viral/genética , Ligação Proteica , AnimaisRESUMO
AIM OF THE STUDY: In the context of the worldwide vaccination campaign against COVID-19, France has been deploying multiple sites for mass vaccination. This study aimed to assess the perceived usefulness of a prototype decontamination mobile unit (UMDEO) for COVID-19 vaccination among both the patient and healthcare providers perspectives. METHODS: This was a descriptive cross-sectional study conducted in Toulouse over two days. UMDEO is a fully comprehensive, versatile solution that was deployed as a 5-row vaccination unit. A written questionnaire was distributed from March 6th-7th, 2021 among all patients presenting for vaccination at the mobile center, as well as the team participating in the vaccination campaign. RESULTS: Among the vaccinated patients (n = 1659), 1409 participants (84.9%) filled out the survey, as well as 68 out of 85 (80%) within the UMDEO team. The maximum patient rate was 98 people per hour. The majority of participants and caregivers (1307 [93.2%] and 67 [98.5%] respectively) agreed that the mobile unit increased access to vaccination. A total of 91.3% patients (n = 1281) and 95.6% caregivers (n = 65) believed that it would speed up the overall vaccination campaign. CONCLUSION: The majority of the vaccinated population and of the team participating in the survey were satisfied with the usefulness of UMDEO as a vaccination center. Toulouse is currently the only city to have used such a structure for vaccination, but it could be used as a basis for planning other mobile units to increase vaccination access.