Article
Microbiology
Chongyang Wang, Liuyuan Duan, Ting Wang, Wenbin Wang, Yu Han, Ruochen Hu, Qili Hou, Haijin Liu, Juan Wang, Xinglong Wang, Sa Xiao, Ruyi Dang, Junru Wang, Gaiping Zhang, Zengqi Yang
Summary: In this study, the formation of inclusion bodies (IBs) containing newly synthesized viral RNA in Newcastle disease virus (NDV) infection was investigated. The IBs observed by electron microscopy were not membrane-bound and showed properties consistent with liquid-liquid phase separation (LLPS). The nucleoprotein (NP) and phosphoprotein (P) were found to be sufficient to generate IB-like puncta, with specific domains of NP and the C terminus of P playing important roles in this process.
VETERINARY MICROBIOLOGY
(2023)
Review
Virology
Hortense Decool, Lorene Gonnin, Irina Gutsche, Christina Sizun, Jean-Francois Eleouet, Marie Galloux
Summary: Pneumoviruses, including pathogenic human and animal viruses such as hRSV and hMPV, are major causes of severe respiratory illnesses in young children and vulnerable populations. Transcription and replication of these viruses rely on specific cytoplasmic inclusions and interactions between viral polymerase and cofactors. Recent structural studies on viral proteins aim to aid in the development of new antivirals against these viruses.
Review
Cell Biology
Olga Dolnik, Gesche K. Gerresheim, Nadine Biedenkopf
Summary: Infections by NSVs lead to the formation of viral inclusion bodies with properties of biomolecular condensates, facilitating efficient viral replication.
Article
Biochemistry & Molecular Biology
Yuya Hirai, Masayuki Horie
Summary: Researchers have discovered that Nyamanini virus (NYMV), a tick-borne mononegavirus, forms inclusion bodies (IBs) in the nucleus of infected cells. They found that these IBs consist of condensates and puncta of various sizes and morphologies. Additionally, the expression of NYMV nucleoprotein (N) and phosphoprotein (P) alone can induce the formation of condensates and puncta in the nucleus, respectively.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Simon Jenni, Joshua A. Horwitz, Louis-Marie Bloyet, Sean P. J. Whelan, Stephen C. Harrison
Summary: In this study, the structure of the vesicular stomatitis virus (VSV) was determined using cryogenic electron microscopy. The researchers also investigated the mechanism of self-assembly of the virus. These findings provide valuable insights into the biology of VSV and its related viruses.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Yuya Hirai, Keizo Tomonaga, Masayuki Horie
Summary: This study characterized the inclusion bodies (IBs) of the mononegavirus BoDV-1 in terms of liquid-liquid phase separation (LLPS), revealing that the phosphoprotein (P) alone can induce LLPS and co-expression of nucleoprotein (N) and P is required for IB-like structure formation in cells. Additionally, BoDV-1 P binds to RNA, but excess RNA can dissolve the liquid droplets formed by N and P in vitro.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Virology
Hortense Decool, Benjamin Bardiaux, Luis Checa Ruano, Olivier Sperandio, Jenna Fix, Irina Gutsche, Charles-Adrien Richard, Monika Bajorek, Jean-Francois Eleouet, Marie Galloux
Summary: Human metapneumovirus (HMPV) causes severe respiratory diseases, but the molecular mechanisms involved in viral replication are not fully understood. In this study, researchers investigated the interaction between two major viral proteins involved in HMPV RNA synthesis, and characterized their domains of interaction. They also identified a potential target on the surface of the N protein for the design of antiviral compounds.
JOURNAL OF VIROLOGY
(2022)
Article
Biochemistry & Molecular Biology
Silva Khodjoyan, Deborha Morissette, Fortune Hontonnou, Luis Checa Ruano, Charles-Adrien Richard, Olivier Sperandio, Jean-Francois Eleouet, Marie Galloux, Philippe Durand, Stephanie Deville-Foillard, Christina Sizun
Summary: The interaction between Respiratory Syncytial Virus phosphoprotein P and nucleoprotein N is crucial for the formation of the RSV polymerase. We investigated the binding affinities and dynamics of this interaction using nuclear magnetic resonance and fluorescence polarization. We optimized parameters for a robust RSV N-P inhibition assay and validated it with the M76 molecule for further chemical library screening.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Cedric Diot, Charles-Adrien Richard, Jennifer Risso-Ballester, Davy Martin, Jenna Fix, Jean-Francois Eleouet, Christina Sizun, Marie-Anne Rameix-Welti, Marie Galloux
Summary: Respiratory syncytial virus (RSV) RNA synthesis occurs in membrane-less organelles called inclusion bodies (IBs), driven by liquid-liquid phase separation. Cyclopamine (CPM) inhibits RSV multiplication by disorganizing and hardening IBs. The activity of CPM depends on the viral transcription factor M2-1, and it affects the competition between P and RNA binding to M2-1. These findings suggest that stabilizing viral protein-protein interactions is a promising antiviral approach for RSV.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Immunology
Bianca S. Bodmer, Melina Vallbracht, Dmitry S. Ushakov, Lisa Wendt, Petr Chlanda, Thomas Hoenen
Summary: This study investigates the formation of inclusion bodies (IBs) in Ebola virus (EBOV) and confirms that EBOV IBs are liquid organelles. The oligomerization of EBOV nucleoprotein plays a crucial role in their formation, while VP35 alters their liquid behavior.
EMERGING MICROBES & INFECTIONS
(2023)
Article
Biochemistry & Molecular Biology
Alexander V. Fonin, Sergey A. Silonov, Anna S. Fefilova, Olesya V. Stepanenko, Anastasia A. Gavrilova, Alexey V. Petukhov, Anna E. Romanovich, Anna L. Modina, Tatiana S. Zueva, Evgeniy M. Nedelyaev, Nadejda M. Pleskach, Mirya L. Kuranova, Irina M. Kuznetsova, Vladimir N. Uversky, Konstantin K. Turoverov
Summary: The study revealed that the C-terminal domains of PML isoforms are capable of forming dynamic liquid droplet compartments, regardless of the ordered N-terminal RBCC motifs. This suggests a significant role of non-specific interactions in the liquid-liquid phase separation leading to the formation of PML bodies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Vikas A. Tillu, James Rae, Ya Gao, Nicholas Ariotti, Matthias Floetenmeyer, Oleksiy Kovtun, Kerrie-Ann Mcmahon, Natasha Chaudhary, Robert G. Parton, Brett M. Collins
Summary: The study highlights the essential role of the three disordered domains of Cavin1 in caveola formation and dynamic trafficking, as well as the fuzzy electrostatic interactions between Cavin1 and caveolin-1 proteins, combined with membrane lipid interactions, in generating membrane curvature and maintaining a stable caveola coat.
NATURE COMMUNICATIONS
(2021)
Article
Virology
Xiaofei Dong, Xue Wang, Mengjia Xie, Wei Wu, Zhongzhou Chen
Summary: Human parainfluenza virus 3 (HPIV3) causes annual epidemics of respiratory diseases, especially in newborns and infants. The core components consist of just three viral proteins: nucleoprotein (N), phosphoprotein (P), and RNA polymerase (L). The study revealed the structure of unassembled HPIV3 N-0 in complex with the N-terminal portion of the P, showing that P mainly binds to the C-terminal domain of N-0 by hydrophobic interaction and interferes with the formation of N-RNA oligomers, which could be a potential target for drug development.
JOURNAL OF VIROLOGY
(2022)
Article
Biochemistry & Molecular Biology
Andrea Vandelli, Fernando Cid Samper, Marc Torrent Burgas, Natalia Sanchez De Groot, Gian Gaetano Tartaglia
Summary: Condensation, or liquid-like phase separation, is an important phenomenon for the spatiotemporal regulation of molecules within the cell. Recent studies have shown that components of phase-separated organelles like Stress Granules (SGs) and Processing Bodies (PBs) exhibit high variability and dynamics in their composition and molecular organization. The formation of SGs and PBs is regulated by a dense contact network involving both RNAs and proteins, and the molecular architecture of these organelles is not yet fully understood.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Virology
Rachel Erin Thompson, Kearstin Edmonds, Rebecca Ellis Dutch
Summary: Human metapneumovirus (HMPV) is a negative-strand RNA virus that causes respiratory tract infections. In this study, researchers found that the HMPV phosphoprotein (P) is necessary for the formation of inclusion bodies (IBs) and viral RNA synthesis. The C-terminal domain of P plays a critical role in IB formation and contains potential phosphorylation sites. Mutations to these phosphorylation sites affected RNA synthesis and viral particle production. Understanding these mechanisms could lead to the development of therapeutics for HMPV infection.
JOURNAL OF VIROLOGY
(2023)
Article
Virology
Monika Bajorek, Marie Galloux, Charles-Adrien Richard, Or Szekely, Rina Rosenzweig, Christina Sizun, Jean-Francois Eleouet
Summary: This study investigates the interaction between the matrix (M) and phosphoprotein (P) during respiratory syncytial virus (RSV) assembly and budding, revealing a direct interaction between M and P and identifying novel interaction sites on P. The findings highlight the importance of the tetrameric structural organization of P and the oligomerization domain (OD) for virus-like filament formation and VLP release.
JOURNAL OF VIROLOGY
(2021)
Article
Virology
Maxence Fretaud, Delphyne Descamps, Daphne Laubreton, Marie-Anne Rameix-Welti, Jean-Francois Eleouet, Thibaut Larcher, Marie Galloux, Christelle Langevin
Summary: The combination of tissue clearing, 3D microscopy, and image processing has led to the development of a novel visualization tool for RSV infection in undissected mouse lungs, allowing for the identification of infected cell subtypes and cytoplasmic viral factories. This new method provides unprecedented insights into RSV pathophysiology and enhances 2D histology analyses.
Article
Geriatrics & Gerontology
Yohan Hababou, Assia Taleb, Amelie Recoing, Frederique Moreau, Isabelle Simon, Florence Muller de Schongor, Elyanne Gault, Marie-Anne Rameix-Welti
Summary: Acquired infections in hospitalized elderly people are a growing concern, with virus outbreaks posing a common challenge for infection prevention teams in long-term care facilities. A study in a long-term care hospital in Paris revealed RSV RNA in respiratory samples from 19 patients, with genotyping identifying 12 nosocomial cases in a unique cluster with an average age of 89 for outbreak cases.
Letter
Critical Care Medicine
Djillali Annane, Martin Rottman, Nicholas Heming, Veronique Godot, Jerome Fleuriet, Jean Sebastien Blanchet, Pierre Moine, Lamiae Grimaldi, Sylvie Chevret
INTENSIVE CARE MEDICINE
(2021)
Article
Multidisciplinary Sciences
Jennifer Risso-Ballester, Marie Galloux, Jingjing Cao, Ronan Le Goffic, Fortune Hontonnou, Aude Jobart-Malfait, Aurore Desquesnes, Svenja M. Sake, Sibylle Haid, Miaomiao Du, Xiumei Zhang, Huanyun Zhang, Zhaoguo Wang, Vincent Rincheval, Youming Zhang, Thomas Pietschmann, Jean-Francois Eleouet, Marie-Anne Rameix-Welti, Ralf Altmeyer
Summary: The study demonstrates that cyclopamine and its analogue A3E inhibit RSV replication by disorganizing and hardening inclusion bodies. These small molecules act directly on the liquid properties of inclusion bodies, disrupting them within minutes. Cyclopamine and A3E also inhibit RSV in infected mice, showing in vivo activity as condensate-targeting drugs.
Article
Microbiology
Melanie Brugger, Thomas Demoulins, G. Tuba Barut, Beatrice Zumkehr, Blandina I. Oliveira Esteves, Kemal Mehinagic, Quentin Haas, Aline Schogler, Marie-Anne Rameix-Welti, Jean-Francois Eleouet, Ueli Moehrlen, Thomas M. Marti, Ralph A. Schmid, Artur Summerfield, Horst Posthaus, Nicolas Ruggli, Sean R. R. Hall, Marco P. Alves
Summary: The research highlights the critical role of lung-resident MSCs in virus-induced acute lung injury, showing their involvement in immune response, repair mechanisms, and expansion of the pulmonary MSC pool following infection. These findings contribute to a better understanding of host response and lung repair mechanisms, with potential therapeutic implications.
Article
Immunology
Emilie Jacque, Claire Chottin, Daphne Laubreton, Michel Nogre, Cecile Ferret, Sandrine de Marcos, Linda Baptista, Carole Drajac, Philippe Mondon, Christophe De Romeuf, Marie-Anne Rameix-Welti, Jean-Francois Eleouet, Sami Chtourou, Sabine Riffault, Gerald Perret, Delphyne Descamps
Summary: The article introduces a new type of anti-respiratory syncytial virus (RSV) immunoglobulin, manufactured through an innovative bioprocess, with high purity and concentration, and strong neutralizing effects on the virus. Experimental results show that low doses of hyper-enriched anti-RSV IgG can be administered locally to ensure rapid and efficient inhibition of virus infection, which may have promising applications in preventing and treating other infectious diseases.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Lorene Gonnin, Charles-Adrien Richard, Irina Gutsche, Didier Chevret, Joris Troussier, Jean-Jacques Vasseur, Francoise Debart, Jean-Francois Eleoue, Marie Galloux
Summary: Respiratory syncytial virus has a negative-sense single-stranded RNA genome encapsidated by the viral nucleoprotein N. The recruitment of L protein onto the nucleoprotein depends on the viral phosphoprotein P. The interaction between P and N complexed with RNA is responsible for the morphogenesis of viral factories.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Microbiology
Gina Cosentino, Katherine Marougka, Aurore Desquesnes, Nicolas Welti, Delphine Sitterlin, Elyanne Gault, Marie-Anne Rameix-Welti
Summary: This study reveals that RSV RNPs move within cells by utilizing microtubules and the endosome recycling pathway, shedding light on the transportation mechanism of vRNPs.
Article
Infectious Diseases
Matthieu Receveur, Michele Ottmann, Jean-Marc Reynes, Jean-Francois Eleouet, Marie Galloux, Aurore Receveur, Dominique Ploin, Sylvie Fiorini, Nathalie Rivat, Martine Valette, Bruno Lina, Jean-Sebastien Casalegno
Summary: This study investigated the association between maternal antibody titers against the RSV nucleoprotein (N protein) at birth and the risk of newborns developing very severe lower respiratory tract infection (VS-LRTI). The results showed that the antibody titers were significantly lower in newborns with risk factors for RSV severe LRTI, but there was no association between antibody titer and protection against VS-LRTI. Further studies are needed to determine if transfer of maternal antibodies against RSV N protein can provide early immune protection in infants.
INFLUENZA AND OTHER RESPIRATORY VIRUSES
(2023)
Article
Biochemistry & Molecular Biology
Silva Khodjoyan, Deborha Morissette, Fortune Hontonnou, Luis Checa Ruano, Charles-Adrien Richard, Olivier Sperandio, Jean-Francois Eleouet, Marie Galloux, Philippe Durand, Stephanie Deville-Foillard, Christina Sizun
Summary: The interaction between Respiratory Syncytial Virus phosphoprotein P and nucleoprotein N is crucial for the formation of the RSV polymerase. We investigated the binding affinities and dynamics of this interaction using nuclear magnetic resonance and fluorescence polarization. We optimized parameters for a robust RSV N-P inhibition assay and validated it with the M76 molecule for further chemical library screening.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Cedric Diot, Charles-Adrien Richard, Jennifer Risso-Ballester, Davy Martin, Jenna Fix, Jean-Francois Eleouet, Christina Sizun, Marie-Anne Rameix-Welti, Marie Galloux
Summary: Respiratory syncytial virus (RSV) RNA synthesis occurs in membrane-less organelles called inclusion bodies (IBs), driven by liquid-liquid phase separation. Cyclopamine (CPM) inhibits RSV multiplication by disorganizing and hardening IBs. The activity of CPM depends on the viral transcription factor M2-1, and it affects the competition between P and RNA binding to M2-1. These findings suggest that stabilizing viral protein-protein interactions is a promising antiviral approach for RSV.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Virology
Hortense Decool, Benjamin Bardiaux, Luis Checa Ruano, Olivier Sperandio, Jenna Fix, Irina Gutsche, Charles-Adrien Richard, Monika Bajorek, Jean-Francois Eleouet, Marie Galloux
Summary: Human metapneumovirus (HMPV) causes severe respiratory diseases, but the molecular mechanisms involved in viral replication are not fully understood. In this study, researchers investigated the interaction between two major viral proteins involved in HMPV RNA synthesis, and characterized their domains of interaction. They also identified a potential target on the surface of the N protein for the design of antiviral compounds.
JOURNAL OF VIROLOGY
(2022)