The Intrinsically Disordered W Protein Is Multifunctional during Henipavirus Infection, Disrupting Host Signalling Pathways and Nuclear Import.
Active Transport, Cell Nucleus
/ immunology
Hendra Virus
/ metabolism
Henipavirus Infections
/ immunology
Host Microbial Interactions
/ immunology
Humans
Immunity, Innate
Interferons
/ metabolism
Intrinsically Disordered Proteins
/ chemistry
Nipah Virus
/ metabolism
Nuclear Envelope
/ metabolism
Receptors, Pattern Recognition
/ metabolism
Signal Transduction
/ immunology
Viral Proteins
/ chemistry
IRF-3
STAT
W protein
henipaviruses
intrinsically disordered
Journal
Cells
ISSN: 2073-4409
Titre abrégé: Cells
Pays: Switzerland
ID NLM: 101600052
Informations de publication
Date de publication:
18 08 2020
18 08 2020
Historique:
received:
13
06
2020
revised:
10
08
2020
accepted:
13
08
2020
entrez:
23
8
2020
pubmed:
23
8
2020
medline:
20
3
2021
Statut:
epublish
Résumé
Nipah and Hendra viruses are highly pathogenic, zoonotic henipaviruses that encode proteins that inhibit the host's innate immune response. The W protein is one of four products encoded from the P gene and binds a number of host proteins to regulate signalling pathways. The W protein is intrinsically disordered, a structural attribute that contributes to its diverse host protein interactions. Here, we review the role of W in innate immune suppression through inhibition of both pattern recognition receptor (PRR) pathways and interferon (IFN)-responsive signalling. PRR stimulation leading to activation of IRF-3 and IFN release is blocked by henipavirus W, and unphosphorylated STAT proteins are sequestered within the nucleus of host cells by W, thereby inhibiting the induction of IFN stimulated genes. We examine the critical role of nuclear transport in multiple functions of W and how specific binding of importin-alpha (Impα) isoforms, and the 14-3-3 group of regulatory proteins suggests further modulation of these processes. Overall, the disordered nature and multiple functions of W warrant further investigation to understand henipavirus pathogenesis and may reveal insights aiding the development of novel therapeutics.
Identifiants
pubmed: 32824665
pii: cells9081913
doi: 10.3390/cells9081913
pmc: PMC7465373
pii:
doi:
Substances chimiques
Intrinsically Disordered Proteins
0
Receptors, Pattern Recognition
0
Viral Proteins
0
Interferons
9008-11-1
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Commentaires et corrections
Type : ErratumIn
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