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The NSs protein encoded by the virulent strain of Rift Valley fever virus targets the expression of Abl2 and the actin cytoskeleton of the host affecting cell mobility, cell shape and cell-cell adhesion

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  • معلومة اضافية
    • Contributors:
      Centre interdisciplinaire chimie biologie-Paris (CICB-Paris FR3567); Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie - CNRS Chimie (INC-CNRS)-Centre National de la Recherche Scientifique (CNRS); Virologie Structurale - Structural Virology; Institut Pasteur Paris (IP)-Centre National de la Recherche Scientifique (CNRS); Institut Cochin (IC UM3 (UMR 8104 / U1016)); Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité); Génétique fonctionnelle de la Souris; Agence Nationale de la Recherche (ANR) provided funding to Eliette Bonnefoy, Marie Flamand, and Jean-Jacques Panthier under grant number ANR-11-BSV3-007. The DIM-Malinf project from Région Ile-de-France provided funding to Vasco Marcato.; ANR-11-BSV3-0007,GenRift,Identification de voies cellulaires et de gènes clés pour la pathogénicité et la résistance au virus de la fièvre de la Vallée du Rift(2011)
    • بيانات النشر:
      HAL CCSD
      American Society for Microbiology
    • الموضوع:
      2020
    • Collection:
      Institut Pasteur: HAL
    • نبذة مختصرة :
      International audience ; Rift Valley fever virus (RVFV) is a highly pathogenic zoonotic arbovirus endemic in many African countries and the Arabian Peninsula. Animal infections cause high rates of mortality and abortion among sheep, goats, and cattle. In humans, an estimated 1 to 2% of RVFV infections result in severe disease (encephalitis, hepatitis, or retinitis) with a high rate of lethality when associated with hemorrhagic fever. The RVFV NSs protein, which is the main virulence factor, counteracts the host innate antiviral response to favor viral replication and spread. However, the mechanisms underlying RVFV-induced cytopathic effects and the role of NSs in these alterations remain for the most part unknown. In this work, we have analyzed the effects of NSs expression on the actin cytoskeleton while conducting infections with the NSs-expressing virulent (ZH548) and attenuated (MP12) strains of RVFV and the non-NSs-expressing avirulent (ZH548ΔNSs) strain, as well as after the ectopic expression of NSs. In macrophages, fibroblasts, and hepatocytes, NSs expression prevented the upregulation of Abl2 (a major regulator of the actin cytoskeleton) expression otherwise induced by avirulent infections and identified here as part of the antiviral response. The presence of NSs was also linked to an increased mobility of ZH548-infected cells compared to ZH548ΔNSs-infected fibroblasts and to strong changes in cell morphology in nonmigrating hepatocytes, with reduction of lamellipodia, cell spreading, and dissolution of adherens junctions reminiscent of the ZH548-induced cytopathic effects observed in vivo. Finally, we show evidence of the presence of NSs within long actin-rich structures associated with NSs dissemination from NSs-expressing toward non-NSs-expressing cells.IMPORTANCE: Rift Valley fever virus (RVFV) is a dangerous human and animal pathogen that was ranked by the World Health Organization in 2018 as among the eight pathogens of most concern for being likely to cause wide epidemics in the near future and ...
    • Relation:
      info:eu-repo/semantics/altIdentifier/pmid/33087469; hal-03042551; https://hal.science/hal-03042551; https://hal.science/hal-03042551/document; https://hal.science/hal-03042551/file/Bamia%202020.pdf; PUBMED: 33087469; PUBMEDCENTRAL: PMC7737741
    • الرقم المعرف:
      10.1128/JVI.01768-20
    • الدخول الالكتروني :
      https://hal.science/hal-03042551
      https://hal.science/hal-03042551/document
      https://hal.science/hal-03042551/file/Bamia%202020.pdf
      https://doi.org/10.1128/JVI.01768-20
    • Rights:
      http://creativecommons.org/licenses/by-nc/ ; info:eu-repo/semantics/OpenAccess
    • الرقم المعرف:
      edsbas.CC775A44