MC159 of Molluscum Contagiosum Virus Suppresses Autophagy by Recruiting Cellular SH3BP4 via an SH3 Domain-Mediated Interaction.


Journal

Journal of virology
ISSN: 1098-5514
Titre abrégé: J Virol
Pays: United States
ID NLM: 0113724

Informations de publication

Date de publication:
15 05 2019
Historique:
received: 12 09 2018
accepted: 20 02 2019
pubmed: 8 3 2019
medline: 3 3 2020
entrez: 8 3 2019
Statut: epublish

Résumé

MC159 is a viral FLIP (FLICE inhibitory protein) encoded by the molluscum contagiosum virus (MCV) enabling MCV to evade antiviral immunity and to establish persistent infections in humans. Here, we show that MC159 contains a functional SH3 binding motif, which mediates avid and selective binding to SH3BP4, a signaling protein known to regulate endocytic trafficking and suppress cellular autophagy. The capacity to bind SH3BP4 was dispensable for regulation of NF-κB-mediated transcription and suppression of proapoptotic caspase activation but contributed to inhibition of amino acid starvation-induced autophagy by MC159. These results provide new insights into the cellular functions of MC159 and reveal SH3BP4 as a novel host cell factor targeted by a viral immune evasion protein.

Identifiants

pubmed: 30842330
pii: JVI.01613-18
doi: 10.1128/JVI.01613-18
pmc: PMC6498068
pii:
doi:

Substances chimiques

Adaptor Proteins, Signal Transducing 0
NF-kappa B 0
SH3BP4 protein, human 0
Viral Proteins 0
viral FLIP protein, Molluscum contagiosum virus 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2019 American Society for Microbiology.

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Auteurs

Constanze Schmotz (C)

Department of Virology, University of Helsinki, Helsinki University Hospital, Helsinki, Finland.

Hasan Uğurlu (H)

Department of Virology, University of Helsinki, Helsinki University Hospital, Helsinki, Finland.

Silja Vilen (S)

Department of Virology, University of Helsinki, Helsinki University Hospital, Helsinki, Finland.

Subhash Shrestha (S)

Department of Virology, University of Helsinki, Helsinki University Hospital, Helsinki, Finland.

Riku Fagerlund (R)

Department of Virology, University of Helsinki, Helsinki University Hospital, Helsinki, Finland.

Kalle Saksela (K)

Department of Virology, University of Helsinki, Helsinki University Hospital, Helsinki, Finland kalle.saksela@helsinki.fi.

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