PXD025339-1

PXD025339 is an original dataset announced via ProteomeXchange.

Title	Adenovirus remodeling of the host proteome and of host factors associating with viral genomes
Description	Viral infections are associated with extensive remodeling of the cellular proteome. Viruses encode gene products that manipulate host proteins to redirect cellular processes or subvert antiviral immune responses. One way in which host antiviral proteins antagonize viral infection is by associating with viral genomes and inhibiting essential viral processes. Adenovirus (AdV) encodes gene products from the early E4 region which are necessary for productive infection. Some cellular antiviral proteins are known to be targeted by AdV E4 gene products, resulting in their degradation or mislocalization. However, the full repertoire of host proteins manipulated by viral E4 proteins has not been defined. To identify cellular proteins and processes manipulated by viral products, we developed a global, un-biased proteomics approach to analyze changes to the host proteome during infection with Adenovirus serotype 5 (Ad5) virus. We combined quantification of total protein abundance in the proteome together with an analysis of proteins associated with viral genomes using isolation of Proteins on Nascent DNA (iPOND). By Integrating these proteomics datasets, we identified cellular factors that are degraded in an E4-dependent manner or are associated with the viral genome in the absence of E4 proteins. We further show that some identified proteins exert inhibitory effects on Ad5 infection. Our systems-level analysis reveals cellular processes that are manipulated during Ad5 infection and points to host factors counteracted by early viral proteins as they remodel the host proteome to promote efficient infection. Importance Viral infections stimulate myriad changes to the host cell proteome. As viruses harness cellular processes and counteract host defenses, they impact abundance, modifications, or localization of cellular proteins. Elucidating the dynamic changes to the cellular proteome during viral replication is integral to understanding how virus-host interactions influence the outcome of infection. Adenovirus serotype 5 (Ad5) encodes early gene products from the E4 genomic region that are known to alter host response pathways and promote replication, but the full extent of proteome modifications they mediate is not known. We use an integrated proteomics approach to quantitate protein abundance and protein associations with viral DNA during virus infection. Systems-level analysis identifies cellular proteins and processes impacted in an E4-dependent manner that could overcome potentially inhibitory host defenses. This study provides a global view of Adenovirus-mediated proteome remodeling which can serve as a model to investigate virus-host interactions of DNA viruses.
HostingRepository	PRIDE
AnnounceDate	2021-08-11
AnnouncementXML	Submission_2021-08-11_03:37:13.753.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD025339
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Katarzyna Kulej
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion; LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2021-04-12 20:07:00	ID requested
⏵ 1	2021-08-11 03:37:14	announced

Dataset with its publication pending

submitter keyword: virus infection, intrinsic defense, Adenovirus, DNA virus, iPOND

Benjamin A. Garcia
contact affiliation	Department of Biochemistry and Biophysics Smilow Center for Translational Research Perelman School of Medicine University of Pennsylvania 3400 Civic Center Blvd Philadelphia, PA 19104
contact email	bgarci@pennmedicine.upenn.edu
lab head
Katarzyna Kulej
contact affiliation	Children's Hospital of Philadelphia
contact email	kulej.katarzyna@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD025339
     1. Label: PRIDE project
     2. Name: Adenovirus remodeling of the host proteome and of host factors associating with viral genomes