Polymerase-tagged respiratory syncytial virus reveals a dynamic rearrangement of the ribonucleocapsid complex during infection.

Autor: Blanchard EL; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, United States of America., Braun MR; Department of Microbiology, Boston University School of Medicine, Boston, MA, United States of America., Lifland AW; Institute of Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, United States of America., Ludeke B; Department of Microbiology, Boston University School of Medicine, Boston, MA, United States of America., Noton SL; Department of Microbiology, Boston University School of Medicine, Boston, MA, United States of America., Vanover D; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, United States of America., Zurla C; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, United States of America., Fearns R; Department of Microbiology, Boston University School of Medicine, Boston, MA, United States of America., Santangelo PJ; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, United States of America.
Jazyk: angličtina
Zdroj: PLoS pathogens [PLoS Pathog] 2020 Oct 08; Vol. 16 (10), pp. e1008987. Date of Electronic Publication: 2020 Oct 08 (Print Publication: 2020).
DOI: 10.1371/journal.ppat.1008987
Abstrakt: The ribonucleocapsid complex of respiratory syncytial virus (RSV) is responsible for both viral mRNA transcription and viral replication during infection, though little is known about how this dual function is achieved. Here, we report the use of a recombinant RSV virus with a FLAG-tagged large polymerase protein, L, to characterize and localize RSV ribonucleocapsid structures during the early and late stages of viral infection. Through proximity ligation assays and super-resolution microscopy, viral RNA and proteins in the ribonucleocapsid complex were revealed to dynamically rearrange over time, particularly between 6 and 8 hours post infection, suggesting a connection between the ribonucleocapsid structure and its function. The timing of ribonucleocapsid rearrangement corresponded with an increase in RSV genome RNA accumulation, indicating that this rearrangement is likely involved with the onset of RNA replication and secondary transcription. Additionally, early overexpression of RSV M2-2 from in vitro transcribed mRNA was shown to inhibit virus infection by rearranging the ribonucleocapsid complex. Collectively, these results detail a critical understanding into the localization and activity of RSV L and the ribonucleocapsid complex during RSV infection.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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