PXD006426

PXD006426 is an original dataset announced via ProteomeXchange.

Title	Cowpox virus proteomics reveals massive ubiquitination and proteasomal degradation of viral proteins but stable virus cores
Description	The ubiquitin-proteasome system (UPS) is essential for replication of Orthopoxviruses (OPV) like vaccinia and cowpox virus (CPXV). Although several proteome studies identified ubiquitin as part of OPV particles, distinct modification sites are largely unknown. Moreover, the UPS plays a key role in poxvirus core uncoating but the underlying mechanisms are still elusive. In the presented study we show that impairment of CPXV replication by proteasome inhibition is caused by a lack of uncoating which can be observed by electron microscopy. These results suggest, that UPS-dependent degradation of viral core proteins is the mechanism underlying CPXV genome uncoating. To proof this hypothesis we analyzed the mature virion ubiquitinome of CPXV using mass spectrometry (MS). We elucidated 137 conserved ubiquitination sites in 54 viral proteins among five CPXV strains verifying ubiquitin is a major poxvirus modification. Structural core proteins were massively ubiquitinated and virions contained large amounts of K48-linked polyubiquitin supporting the hypothesis. Hence, we aimed to show the proteasome-dependent degradation of CPXV core proteins in infected HeLa cells. However, using MS-based quantitative analysis of ubiquitinated virus proteins early in infection we were not able to show the degradation of viral core proteins. Instead, our results revealed the proteasomal degradation of viral proteins associated with the formation of prereplication sites early in infection.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:37:09.998.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Marica Grossegesse
SpeciesList	scientific name: Cowpox virus; NCBI TaxID: NCBITaxon:10243; scientific name: Cowpox virus (CPV); NCBI TaxID: 10243;
ModificationList	ubiquitination signature dipeptidyl lysine
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2017-05-02 05:44:43	ID requested
1	2018-02-09 11:41:36	announced
⏵ 2	2024-10-22 04:37:13	announced	2024-10-22: Updated project metadata.

10.1038/s41598-018-20130-9;

Grossegesse M, Doellinger J, Fritsch A, Laue M, Piesker J, Schaade L, Nitsche A, Global ubiquitination analysis reveals extensive modification and proteasomal degradation of cowpox virus proteins, but preservation of viral cores. Sci Rep, 8(1):1807(2018) [pubmed]

submitter keyword: Ubiquitination, viral proteomics,Orthopoxvirus

Andreas Nitsche
contact affiliation	ZBS1, Highly Pathogenic Viruses, Robert Koch-Institute, Germany
contact email	NitscheA@rki.de
lab head
Marica Grossegesse
contact affiliation	Robert Koch Institute
contact email	grossegessem@rki.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD006426
     1. Label: PRIDE project
     2. Name: Cowpox virus proteomics reveals massive ubiquitination and proteasomal degradation of viral proteins but stable virus cores