Interactions of viral proteins from pathogenic and low or non-pathogenic orthohantaviruses with human type I interferon signaling

Gallo, G. et al. (2021) Interactions of viral proteins from pathogenic and low or non-pathogenic orthohantaviruses with human type I interferon signaling. Viruses, 13(1), 140. (doi: 10.3390/v13010140) (PMID:33478127) (PMCID:PMC7835746)

Abstract

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.

• Item Type: Articles
• Additional Information: Funding: G.G. was granted by Sorbonne Université ED 515 (n° 2496/2016) and within an INNOV FLASH START Program from DARRI, Institut Pasteur. A.Kwere funded from grants of UK Medical Research Council (MRC) MC_UU_12014/8, and A.D.S.F. and Q.G. from MRC grant MC_UU_12014/12. F.B. acknowledges intramural funding by Friedrich-Loeffler-Institut.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Szemiel, Dr Agnieszka and Da Silva Filipe, Dr Ana and Gu, Dr Quan and Kohl, Professor Alain

Creator Roles

Szemiel, A.: Methodology, Formal analysis
Gu, Q.: Methodology, Data curation
Da Silva Filipe, A.: Methodology, Data curation
Kohl, A.: Conceptualization, Formal analysis, Writing – review and editing, Funding acquisition

• Authors: Gallo, G., Caignard, G., Badonnel, K., Chevreux, G., Terrier, S., Szemiel, A., Roman-Sosa, G., Binder, F., Gu, Q., Da Silva Filipe, A., Ulrich, R. G., Kohl, A., Vitour, D., Tordo, N., and Ermonval, M.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity; College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
• Journal Name: Viruses
• Publisher: MDPI
• ISSN: 1999-4915
• ISSN (Online): 1999-4915
• Copyright Holders: Copyright © 2021 by the authors
• First Published: First published in Viruses 13(1):140
• Publisher Policy: Reproduced under a Creative Commons license

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
65655	1	Arbovirus interactions with arthropod hosts	Alain Kohl	Medical Research Council (MRC)	MC_UU_12014/8	MVLS III - CENTRE FOR VIRUS RESEARCH
		Viral Genomics and Bioinformatics	Andrew Davison	Medical Research Council (MRC)	MC_UU_12014/12	III-MRC-GU Centre for Virus Research