Characterisation of the Semliki Forest Virus-host cell interactome reveals the viral capsid protein as an inhibitor of nonsense-mediated mRNA decay

The positive-sense, single-stranded RNA alphaviruses pose a potential epidemic threat. Understanding the complex interactions between the viral and the host cell proteins is crucial for elucidating the mechanisms underlying successful virus replication strategies and for developing specific antivira...

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Bibliographic Details
Published in:PLoS pathogens 2021-05, Vol.17 (5), p.e1009603-e1009603
Main Authors: Contu, Lara, Balistreri, Giuseppe, Domanski, Michal, Uldry, Anne-Christine, Mühlemann, Oliver
Format: Article
Language:English
Subjects:
Biology and Life Sciences
Capsid protein
Computer and Information Sciences
Double-stranded RNA
eIF-2 kinase
Encephalitis
Epidemics
Flow charts
Genetic aspects
Genomes
Glycoproteins
Health aspects
Host-virus relationships
Infections
Initiation factor eIF-2
Intermediates
Kinases
Mammalian cells
Mass spectrometry
Mass spectroscopy
Medicine and Health Sciences
mRNA turnover
Nonsense-mediated mRNA decay
Phosphorylation
Polyadenine
Polyadenylation
Protein kinase
Protein-protein interactions
Proteins
Proteomes
Research and Analysis Methods
RNA polymerase
Scientific imaging
Semliki Forest virus
Spectroscopy
Viral infections
Viral proteins
Virulence (Microbiology)
Viruses
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Summary:The positive-sense, single-stranded RNA alphaviruses pose a potential epidemic threat. Understanding the complex interactions between the viral and the host cell proteins is crucial for elucidating the mechanisms underlying successful virus replication strategies and for developing specific antiviral interventions. Here we present the first comprehensive protein-protein interaction map between the proteins of Semliki Forest Virus (SFV), a mosquito-borne member of the alphaviruses, and host cell proteins. Among the many identified cellular interactors of SFV proteins, the enrichment of factors involved in translation and nonsense-mediated mRNA decay (NMD) was striking, reflecting the virus’ hijacking of the translation machinery and indicating viral countermeasures for escaping NMD by inhibiting NMD at later time points during the infectious cycle. In addition to observing a general inhibition of NMD about 4 hours post infection, we also demonstrate that transient expression of the SFV capsid protein is sufficient to inhibit NMD in cells, suggesting that the massive production of capsid protein during the SFV reproduction cycle is responsible for NMD inhibition.
ISSN:1553-7374
1553-7366
1553-7374
DOI:10.1371/journal.ppat.1009603