Interactions of Viral Proteins from Pathogenic and Low or Non-Pathogenic Orthohantaviruses with Human Type I Interferon Signaling

Viruses

Karine Badonnel¹  Florian Binder²  RainerG. Ulrich²  Guillaume Chevreux³  Samuel Terrier³  Gleyder Roman-Sosa⁴  Giulia Gallo⁵  Noël Tordo⁵  Myriam Ermonval⁵  Ana Da Silva Filipe⁶  Agnieszka Szemiel⁶  Alain Kohl⁶  Quan Gu⁶  Grégory Caignard⁷  Damien Vitour⁷ 

[1] BREED, INRAE, Université Paris-Saclay, 78350 Jouy-en-Josas, France;Friedrich-Loeffler-Institut, Institute of Novel and Emerging Infectious Diseases, 17493 Greifswald-Insel Riems, Germany;Institut Jacques Monod, CNRS UMR 7592, ProteoSeine Mass Spectrometry Plateform, Université de Paris, 75013 Paris, France;Institut Pasteur, Unité de Biologie Structurale, 75015 Paris, France;Institut Pasteur, Unité des Stratégies Antivirales, 75015 Paris, France;MRC-University of Glasgow Centre for Virus Research, Glasgow G61 1QH, UK;UMR 1161 Virologie, Anses-INRAE-EnvA, 94700 Maisons-Alfort, France;

关键词: orthohantavirus;    interferon response;    nonstructural protein;    glycoprotein;    Puumala virus;    Tula virus;   

DOI  :  10.3390/v13010140

来源: DOAJ

【 摘 要 】

Rodent-borne orthohantaviruses are asymptomatic in their natural reservoir, but they can cause severe diseases in humans. Although an exacerbated immune response relates to hantaviral pathologies, orthohantaviruses have to antagonize the antiviral interferon (IFN) response to successfully propagate in infected cells. We studied interactions of structural and nonstructural (NSs) proteins of pathogenic Puumala (PUUV), low-pathogenic Tula (TULV), and non-pathogenic Prospect Hill (PHV) viruses, with human type I and III IFN (IFN-I and IFN-III) pathways. The NSs proteins of all three viruses inhibited the RIG-I-activated IFNβ promoter, while only the glycoprotein precursor (GPC) of PUUV, or its cleavage product Gn/Gc, and the nucleocapsid (N) of TULV inhibited it. Moreover, the GPC of both PUUV and TULV antagonized the promoter of IFN-stimulated responsive elements (ISRE). Different viral proteins could thus contribute to inhibition of IFNβ response in a viral context. While PUUV and TULV strains replicated similarly, whether expressing entire or truncated NSs proteins, only PUUV encoding a wild type NSs protein led to late IFN expression and activation of IFN-stimulated genes (ISG). This, together with the identification of particular domains of NSs proteins and different biological processes that are associated with cellular proteins in complex with NSs proteins, suggested that the activation of IFN-I is probably not the only antiviral pathway to be counteracted by orthohantaviruses and that NSs proteins could have multiple inhibitory functions.

【 授权许可】

Unknown