@INRAE-Nicolas Bertrand (Coloration de lame avant l'observation au microscope dans l'UMR (ANSES-INRA-ENVA) de biologie moléculaire et immunologie parasitaire à l'ENVA de Maisons-Alfort.)

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A condensate-hardening drug blocks RSV replication in vivo in Nature on 07 July 2021

In this article we show the action of an antiviral compound targetting the respiratory syncytial virus, a pneumovirus responsible for brochiolitis and pneumonia in young children and calves. This studied involved a three-team partnership: the teams directed by Ralf Altmeyer (Shandong University, China), Marie-Anne Raleix-Welti (UVSQ- U. Paris-Saclay) and J.-F. Eléouët (VIM, INRAE, U. Paris-Saclay).

Pneumoviruses are responsible for respiratory diseases that can be severe (bronchiolitis, pneumonia) in man and animals; they infect the epithelial cells of the host and induce the formation of inclusion bodies (IB) in cells. These IB are viral factories where RNA is synthesized. They form by the exclusion of the liquid phase a little like droplets of oil in water but are organized by protein-protein or protein-RNA interactions with generally the implification of proteins with disordered domains. These organelles have no membrane and are located in the cells and their nucleus: nucleoli, stress granules etc. We identified a molecule, cyclopamine (CPM), that disturbs these viral structures. We show that CPM disorganizes the IB by changing their physical-chemical properties and notably by hardening these liquid droplets. In addition, we have separated the toxic action of CPM (activation of the Hedgehog pathway) on the cell from that tareting the virus.

Reference: https://www.nature.com/articles/s41586-021-03703-z
DOI : 10.1038/s41586-021-03703-z.

Contact : Jean-François Eléouët
Jean-francois.eleouet@inrae.fr

See also

Physical Principles Underlying the Complex Biology of Intracellular Phase Transitions. Choi JM, et al. Annu Rev Biophys. 2020. PMID: 32004090 Review.

New Perspectives on the Biogenesis of Viral Inclusion Bodies in Negative-Sense RNA Virus Infections. Dolnik O, Gerresheim GK, Biedenkopf N.Cells. 2021 Jun 10;10(6):1460. doi: 10.3390/cells10061460.

Modification date : 02 November 2023 | Publication date : 09 July 2021 | Redactor : Jean-François Eléouët - Edition P. Huan - Translation W. Brand-Williams