Infection of Human Endothelial Cells with Lassa Virus Induces Early but Transient Activation and Low Type I IFN Response Compared to the Closely-Related Nonpathogenic Mopeia Virus.

Autor: Merabet O; Unité de Biologie des Infections Virales Emergentes, Institut Pasteur, 69007 Lyon, France.; Centre International de Recherche en Infectiologie (CIRI), Université de Lyon, INSERM U1111, Ecole Normale Supérieure de Lyon, Université Lyon 1, CNRS, UMR5308, 69007 Lyon, France., Pietrosemoli N; Bioinformatics and Biostatistics Hub, Institut Pasteur, Université de Paris, 75015 Paris, France., Perthame E; Bioinformatics and Biostatistics Hub, Institut Pasteur, Université de Paris, 75015 Paris, France., Armengaud J; Laboratoire Innovations Technologiques pour la Détection et le Diagnostic (LI2D), Service de Pharmacologie et Immunoanalyse (SPI), Commissariat à l'Energie Atomique, 30200 Bagnols-sur-Cèze, France., Gaillard JC; Laboratoire Innovations Technologiques pour la Détection et le Diagnostic (LI2D), Service de Pharmacologie et Immunoanalyse (SPI), Commissariat à l'Energie Atomique, 30200 Bagnols-sur-Cèze, France., Borges-Cardoso V; Unité de Biologie des Infections Virales Emergentes, Institut Pasteur, 69007 Lyon, France.; Centre International de Recherche en Infectiologie (CIRI), Université de Lyon, INSERM U1111, Ecole Normale Supérieure de Lyon, Université Lyon 1, CNRS, UMR5308, 69007 Lyon, France., Daniau M; ViroScan3D SAS, 01600 Trévoux, France., Legras-Lachuer C; ViroScan3D SAS, 01600 Trévoux, France., Carnec X; Unité de Biologie des Infections Virales Emergentes, Institut Pasteur, 69007 Lyon, France.; Centre International de Recherche en Infectiologie (CIRI), Université de Lyon, INSERM U1111, Ecole Normale Supérieure de Lyon, Université Lyon 1, CNRS, UMR5308, 69007 Lyon, France., Baize S; Unité de Biologie des Infections Virales Emergentes, Institut Pasteur, 69007 Lyon, France.; Centre International de Recherche en Infectiologie (CIRI), Université de Lyon, INSERM U1111, Ecole Normale Supérieure de Lyon, Université Lyon 1, CNRS, UMR5308, 69007 Lyon, France.
Jazyk: angličtina
Zdroj: Viruses [Viruses] 2022 Mar 21; Vol. 14 (3). Date of Electronic Publication: 2022 Mar 21.
DOI: 10.3390/v14030652
Abstrakt: Lassa virus (LASV), an Old World arenavirus, is responsible for hemorrhagic fevers in western Africa. The privileged tropism of LASV for endothelial cells combined with a dysregulated inflammatory response are the main cause of the increase in vascular permeability observed during the disease. Mopeia virus (MOPV) is another arenavirus closely related to LASV but nonpathogenic for non-human primates (NHPs) and has never been described in humans. MOPV is more immunogenic than LASV in NHPs and in vitro in human immune cell models, with more intense type I IFN and adaptive cellular responses. Here, we compared the transcriptomic and proteomic responses of human umbilical vein endothelial cells (HUVECs) to infection with the two viruses to further decipher the mechanisms involved in their differences in immunogenicity and pathogenicity. Both viruses replicated durably and efficiently in HUVECs, but the responses they induced were strikingly different. Modest activation was observed at an early stage of LASV infection and then rapidly shut down. By contrast, MOPV induced a late but more intense response, characterized by the expression of genes and proteins mainly associated with the type I IFN response and antigen processing/presentation. Such a response is consistent with the higher immunogenicity of MOPV relative to LASV, whereas the lack of an innate response induced in HUVECs by LASV is consistent with its uncontrolled systemic dissemination through the vascular endothelium.
Databáze: MEDLINE
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