PXD057492

PXD057492 is an original dataset announced via ProteomeXchange.

Title	Usutu virus NS4A induces autophagy and is targeted by the selective autophagy receptor p62/SQSTM1 for degradation
Description	Usutu virus (USUV) is an emerging orthoflavivirus, which mainly affects birds but in rare cases can cause severe neuroinvasive disease in humans. Due to the limited size of the orthoflavivirus genome the virus relies on the host machinery for replication. In addition, it must subvert the host antiviral response for successful replication in the cell. Studying this complex network of virus-host protein interactions by proteomics approaches can provide us new insights in the replication cycle of viruses and can help us better understand the viral pathogenesis. We have previously shown that the USUV protein NS4A acts as an antagonist of the interferon response, and here we further map the host interaction partners of USUV NS4A using proximity labeling coupled to mass spectrometry. The resulting NS4A interactome revealed many host proteins involved in the autophagy pathway. We showed that both USUV infection and overexpression of USUV NS4A can induce the autophagy pathway. However, stimulation or inhibition of the autophagy pathway did not affect USUV replication in general. Therefore, we decided to look specifically at the role of the selective autophagy receptor sequestosome 1 (p62/SQSTM1), which was identified as an interaction partner of USUV NS4A. We found that p62 is involved in the degradation of USUV NS4A. Furthermore, the knockdown of p62 enhanced replication of USUV in A549 cells, which means p62 functions to restrict USUV replication. In conclusion, this study showed that USUV NS4A induced autophagy and was then targeted by p62 for degradation by the autophagic machinery, uncovering a new role of p62 in the antiviral defense against USUV.
HostingRepository	PRIDE
AnnounceDate	2025-05-07
AnnouncementXML	Submission_2025-05-07_04:51:07.271.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Rayman Tjokrodirijo
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2024-11-04 09:23:58	ID requested
⏵ 1	2025-05-07 04:51:08	announced

10.1186/s12985-025-02719-5;

Nelemans T, Tas A, de Beijer NL, Janssen GMC, van Veelen PA, van Hemert MJ, Kikkert M, Usutu virus NS4A induces autophagy and is targeted by the selective autophagy receptor p62/SQSTM1 for degradation. Virol J, 22(1):103(2025) [pubmed]

submitter keyword: orthoflavivirus, autophagy,Usutu virus, NS4A, p62

Peter A. van Veelen
contact affiliation	Head Proteomics Group, Leiden University Medical Center, Center for Proteomics and Metabolomics, PO Box 9600, Postal zone P1-Q, 2300 RC Leiden, The Netherlands
contact email	P.A.van_Veelen@lumc.nl
lab head
Rayman Tjokrodirijo
contact affiliation	Leiden University Medical Center, Proteomics group
contact email	R.T.N.Tjokrodirijo@lumc.nl
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD057492
     1. Label: PRIDE project
     2. Name: Usutu virus NS4A induces autophagy and is targeted by the selective autophagy receptor p62/SQSTM1 for degradation