Endoplasmic Reticulum Associated Aminopeptidase 2 (ERAP2) Is Released in the Secretome of Activated MDMs and Reduces in vitro HIV-1 Infection

Frontiers in Immunology
Irma SaulleMara Biasin

Abstract

Background: Haplotype-specific alternative splicing of the endoplasmic reticulum (ER) aminopeptidase type 2 (ERAP2) gene results in either full-length (FL, haplotype A) or alternatively spliced (AS, haplotype B) mRNA. HapA/HapA homozygous (HomoA) subjects show a reduced susceptibility to HIV-1 infection, probably secondary to the modulation of the antigen processing/presenting machinery. ERAP1 was recently shown to be secreted from the plasma membrane in response to activation; we investigated whether ERAP2 can be released as well and if the secreted form of this enzyme retains its antiviral function. Methods: Human monocyte derived macrophages (MDMs) were differentiated from peripheral blood mononuclear cells (PBMCs) isolated from 6 HomoA healthy controls and stimulated with IFNγ and LPS. ERAP2-FL secretion was evaluated by mass spectrometry. PBMCs (14 HomoA and 16 HomoB) and CD8-depleted PBMCs (CD8-PBMCs) (4 HomoA and 4 HomoB) were in vitro HIV-infected in the absence/presence of recombinant human ERAP2-FL (rhERAP2) protein; p24 viral antigen quantification was used to assess viral replication. IFNγ and CD69 mRNA expression, as well as the percentage of perforin-producing CD8+ T Lymphocytes, were analyzed 3 and 7-days post in...Continue Reading

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Citations

Feb 23, 2020·Expert Review of Clinical Immunology·Claudio FeniziaMara Biasin
Mar 19, 2020·Cells·Irma SaulleMara Biasin
Feb 6, 2020·Biological & Pharmaceutical Bulletin·Masafumi TsujimotoYoshikuni Goto
Aug 15, 2020·Frontiers in Immunology·Fabiana PaladiniRosa Sorrentino
Feb 12, 2021·International Journal of Molecular Sciences·Silvia D'AmicoDoriana Fruci
Mar 20, 2021·Scientific Reports·Mara BiasinMario Clerici
Feb 24, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Irma SaulleMara Biasin
May 4, 2021·Frontiers in Genetics·Yueran LiElizabeth J Phillips

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Methods Mentioned

BETA
density gradient centrifugation
PCR
genotyping
protein assay
acetylation
Assay
ELISA
flow-cytometry
flow cytometry

Software Mentioned

MaxQuant
Andromeda
Graphpad
Kaluza
GRAPHPAD PRISM
CFX manager
Gallios

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