PXD061195-1

PXD061195 is an original dataset announced via ProteomeXchange.

Title	Comparative Interactome Profiling of Nonstructural Protein 3 Across SARS-CoV-2 Variants Emerged During the COVID-19 Pandemic
Description	SARS-CoV-2 virus and its variants have proven to be a threat to global health, in part due to their capacity for rapid evolution. SARS-CoV-2 variants that emerged throughout the COVID-19 pandemic exhibited variations in virulence, leading to diminished vaccine protection and modulating disease severity. Research efforts have identified the molecular changes resulting from structural protein variants of SARS-CoV-2, particularly in Spike, that have enhanced infectivity. Yet, investigating variants of nonstructural proteins is equally critical to understand viral evolution and their role in manipulating protein-protein interactions within a host. This study focuses on nonstructural protein 3 (nsp3), a viral papain-like protease (PLpro) critical for viral polyprotein cleavage, which is also implicated in host de-ubiquitylation, ISGylation, and formation of double-membrane vesicles. Using affinity-purification mass spectrometry (AP-MS), we identify differential protein interactions caused by mutations in nsp3. Included are variants identified between 2019-2024: Alpha 20I, Beta20H, Delta21I, Delta21J, Gamma20J, Kappa21B, Lambda21G, Omicron21K, Omicron21L. A small set of amino acid substitutions in the cytosolic fragment and N-terminal region of nsp3 (nsp3.1) could be traced to increased interactions with RNA binding proteins, which are vital in viral replication. Nsp3.1 variants from Omicron 21K and 21L exhibit distinct patterns of host interactor enrichment, setting them apart from five other variants. In contrast, variants of the central region of nsp3 (nsp3.2) containing the PL2pro domain were found to share interactions with protein quality control machinery, including ER-associated degradation (ERAD). In this construct, shared trends in interactor enrichment are observed between Omicron21K and Delta21I, distinguishing them from three other variants. Our study highlights that even a small number of amino acid substitutions can significantly alter the interaction partners. Our study provides a roadmap to track the interaction changes driven by SARS-CoV-2 variant evolution, which is essential for elucidating the ongoing evolutionary arms race between the host and virus.
HostingRepository	PRIDE
AnnounceDate	2025-05-07
AnnouncementXML	Submission_2025-05-07_07:55:15.928.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jake Hermanson
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-02-25 14:38:54	ID requested
⏵ 1	2025-05-07 07:55:16	announced

Garcia Lopez V, Plate L, Comparative Interactome Profiling of Nonstructural Protein 3 Across SARS-CoV-2 Variants Emerged During the COVID-19 Pandemic. Viruses, 17(3):(2025) [pubmed]

10.3390/v17030447;

submitter keyword: virus-host interactions,affinity purification-mass spectrometry, variants, nsp3

Lars Plate
contact affiliation	Department of Biological Sciences, Department of Chemistry, Vanderbilt University. Department of Pathology, Microbiology and Immunology, Vandberbilt University Medical Center
contact email	lars.plate@vanderbilt.edu
lab head
Jake Hermanson
contact affiliation	Vanderbilt University
contact email	jake.hermanson@vanderbilt.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/05/PXD061195

PRIDE project URI

• PRIDE
  1. PXD061195
     1. Label: PRIDE project
     2. Name: Comparative Interactome Profiling of Nonstructural Protein 3 Across SARS-CoV-2 Variants Emerged During the COVID-19 Pandemic