Skip Navigation LinksHome > July 17, 2013 - Volume 27 - Issue 11 > Endoplasmic reticulum aminopeptidase 2 haplotypes play a rol...
doi: 10.1097/QAD.0b013e3283601cee
Basic Science

Endoplasmic reticulum aminopeptidase 2 haplotypes play a role in modulating susceptibility to HIV infection

Biasin, Maraa,*; Sironi, Manuelab,*; Saulle, Irmaa; de Luca, Mariacristinaa; la Rosa, Francescaa; Cagliani, Racheleb; Forni, Diegob; Agliardi, Cristinag; Caputo, Sergio loc; Mazzotta, Francescoc; Trabattoni, Dariaa; Macias, Juand; Pineda, Juan A.d; Caruz, Antonioe; Clerici, Mariof,g

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Objective: 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. As ERAP2 trims peptides loaded on major histocompatibility complex (MHC) class I and CD8+ T lymphocytes protect against viral infections, we analysed its role in resistance to HIV-1 infection.

Methods: ERAP2 polymorphisms were genotyped using a TaqMan probe, and human leukocyte antigen (HLA) typing of class-I HLAB locus was performed by single specific primers-polymerase chain reaction method. To verify whether ERAP2 genotype influences susceptibility to HIV-1 infection in vitro we performed HIV-1 infection assay. We evaluated antigen presentation pathway with PCR array and the viral antigen p24 with ELISA.

Results: Genotype analysis in 104 HIV-1-exposed seronegative individuals (HESNs) exposed to HIV through IDU-HESN and 130 controls from Spain indicated that hapA protects from HIV infection. Meta-analysis with an Italian cohort of sexually exposed HESN yielded a P value of 7.6 × 10–5. HLAB typing indicated that the HLA-B*57 allele is significantly more common than expected among HESN homozygous for haplotype A (homoA). Data obtained in a cohort of 139 healthy Italian controls showed that following in-vitro HIV-1 infection the expression of ERAP2-FL and a number of genes involved in antigen presentation as well as of MHC class I on the surface of CD45+ cells was significantly increased in homoA cells; notably, homoA peripheral blood mononuclear cells, but not isolated CD4+ cells, were less susceptible to HIV-1 infection.

Conclusion: ERAP2 hapA is correlated with resistance to HIV-1 infection, possibly secondarily to its effect on antigen processing and presentation.

© 2013 Lippincott Williams & Wilkins, Inc.


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