PXD023281

PXD023281 is an original dataset announced via ProteomeXchange.

Title	Long-term liver expression of an apolipoprotein A-I mimetic peptide attenuates IFNα-induced inflammation and promotes antiviral activity
Description	Apolipoprotein A-I mimetic peptides are amphipathic alpha-helix peptides that display similar functions to apolipoprotein A-I. Preclinical and clinical studies have demonstrated the safety and efficacy of apolipoprotein A-I mimetic peptides in multiple indications associated with inflammatory processes. In this study, we evaluated the effect of the long-term expression of L37pA in the liver by an adeno-associated virus (AAV-L37pA) on the expression of an adeno-associated virus encoding interferon-alpha (AAV-IFNα). Long-term IFNα expression in the liver leads to lethal hematological toxicity one month after AAV administration. Concomitant administration of AAV-L37pA prevented the lethal toxicity since the IFNα expression was reduced one month after AAV administration by decreasing the expression of IFNα. To identify the mechanism of action of L37pA, a genomic and proteomic analysis was performed fifteen days after AAV administration when a similar level of IFNα and interferon-stimulated genes were observed in mice treated with AAV-IFNα alone and in mice treated with AAV-IFNα and AAV-L37pA. The coexpression of the apolipoprotein A-I mimetic peptide L37pA with IFNα modulated the gene expression program of IFNα, inducing a significant reduction in inflammatory pathways affecting pathogen-associated molecular patterns receptor, dendritic cells, NK cells and Th1 immune response. The proteomic analysis confirmed the impact of the L37pA activity on several inflammatory pathways and indicated an activation of LXR/RXR and PPPARα/γ nuclear receptors. Thus, long-term expression of L37pA induces an anti-inflammatory effect in the liver that allows silencing of IFNα expression mediated by an adeno-associated virus.
HostingRepository	PRIDE
AnnounceDate	2021-09-09
AnnouncementXML	Submission_2021-09-09_15:30:05.852.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD023281
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Antonio Ramos Fernández
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	methylthiolated residue; 2-pyrrolidone-5-carboxylic acid (Glu); 2-pyrrolidone-5-carboxylic acid (Gln); monohydroxylated residue; acetylated residue
Instrument	TripleTOF 5600

Revision	Datetime	Status	ChangeLog Entry
0	2020-12-22 14:08:24	ID requested
⏵ 1	2021-09-09 15:30:06	announced

Fernandez-Sendin M, Di Trani CA, Bella A, Vasquez M, Ardaiz N, Gomar C, Arrizabalaga L, Ciordia S, Corrales FJ, Aranda F, Berraondo P, Long-Term Liver Expression of an Apolipoprotein A-I Mimetic Peptide Attenuates Interferon-Alpha-Induced Inflammation and Promotes Antiviral Activity. Front Immunol, 11():620283(2020) [pubmed]

submitter keyword: Adeno-associated virus, type I IFN, apolipoprotein A-I mimetic peptide, antiviral, liver

Pedro Berraondo
contact affiliation	Program of Immunology and Immunotherapy, Cima Universidad de Navarra, Pamplona, Spain
contact email	pberraondol@unav.es
lab head
Antonio Ramos Fernández
contact affiliation	Proteobotics S.L.
contact email	aramos@proteobotics.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD023281
     1. Label: PRIDE project
     2. Name: Long-term liver expression of an apolipoprotein A-I mimetic peptide attenuates IFNα-induced inflammation and promotes antiviral activity