Inhibition of interferon I induction by non-structural protein NSs of Puumala virus and other vole-associated orthohantaviruses: phenotypic plasticity of the protein and potential functional domains

Autor: Giulia Gallo, Elias Bendl, Florian Binder, Myriam Ermonval, Christine Luttermann, Rainer G. Ulrich, Isabella Eckerle
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Viral Nonstructural Proteins / genetics
Viral Nonstructural Proteins
Virus Replication
Puumala virus
chemistry.chemical_compound
Interferon
Germany
Chlorocebus aethiops
Viral
Promoter Regions
Genetic
chemistry.chemical_classification
ddc:616
Puumala virus / pathogenicity
biology
General Medicine
Transfection
Adaptation
Physiological
Amino acid
Interferon-beta / metabolism
Hemorrhagic Fever with Renal Syndrome
Host-Pathogen Interactions
Interferon Type I
Original Article
Interferon-beta / genetics
Viral Nonstructural Proteins / chemistry
Interferon Type I / genetics
medicine.drug
Gene Expression Regulation
Viral
Interferon Type I / metabolism
Physiological
Viral Nonstructural Proteins / metabolism
Promoter Regions
Eukaryotic translation
Genetic
Virology
Host-Pathogen Interactions / physiology
medicine
Animals
Humans
Puumala virus / physiology
Adaptation
Puumala virus / isolation & purification
Vero Cells
Methionine
Interferon-beta
biology.organism_classification
Open reading frame
HEK293 Cells
chemistry
Gene Expression Regulation
A549 Cells
Mutation
Vero cell
Zdroj: Archives of Virology, Vol. 166, No 11 (2021) pp. 2999-3012
Archives of Virology
ISSN: 0304-8608
Popis: The orthohantavirus Puumala virus (PUUV), which is transmitted by bank voles (Clethrionomys glareolus), and other vole-borne hantaviruses contain in their small (S) genome segment two overlapping open reading frames, coding for the nucleocapsid protein and the non-structural protein NSs, a putative type I interferon (IFN-I) antagonist. To investigate the role of NSs of PUUV and other orthohantaviruses, the expression pattern of recombinant NSs constructs and their ability to inhibit human IFN-I promoter activity were investigated. The NSs proteins of PUUV and related cricetid-borne orthohantaviruses showed strong inhibition of IFN-I promoter induction. We identified protein products originating from three and two methionine initiation codons in the NSs ORF of PUUV during transfection and infection, respectively. The three putative start codons are conserved in all PUUV strains analysed. Translation initiation at these start codons influenced the inhibitory activity of the NSs products, with the wild-type (wt) construct expressing two proteins starting at the first and second methionine and showing strong inhibition activity. Analysis of in vitro-generated variants and naturally occurring PUUV NSs proteins indicated that amino acid variation in the NSs protein is well tolerated, suggesting its phenotypic plasticity. The N-terminal 20-amino-acid region of the NSs protein was found to be associated with strong inhibition and to be highly vulnerable to amino acid exchanges and tag fusions. Infection studies using human, bank vole, and Vero E6 cells did not show obvious differences in the replication capacity of PUUV Sotkamo wt and a strain with a truncated NSs protein (NSs21Stop), showing that the lack of a full-length NSs might be compensated by its N-terminal peptide, as seen in transfection experiments. These results contribute to our understanding of virus-host interactions and highlight the importance of future innate immunity studies in reservoir hosts. Supplementary Information The online version contains supplementary material available at 10.1007/s00705-021-05159-y.
Databáze: OpenAIRE
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