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

Mara Biasin, Manuela Sironi, Irma Saulle, Mariacristina De Luca, Francesca La Rosa, Rachele Cagliani, Diego Forni, Cristina Agliardi, Sergio Lo Caputo, Francesco Mazzotta, Daria Trabattoni, Juan Macias, Juan A. Pineda, Antonio Caruz, Mario Clerici

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)1697-1706
Number of pages10
JournalAIDS (London, England)
Volume27
Issue number11
DOIs
Publication statusPublished - Jul 17 2013

Keywords

  • antigen presentation
  • endoplasmic reticulum aminopeptidase type 2
  • HIV-1-exposed seronegative individual
  • HIV-infection
  • resistance

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Fingerprint Dive into the research topics of 'Endoplasmic reticulum aminopeptidase 2 haplotypes play a role in modulating susceptibility to HIV infection'. Together they form a unique fingerprint.

  • Cite this

    Biasin, M., Sironi, M., Saulle, I., De Luca, M., La Rosa, F., Cagliani, R., Forni, D., Agliardi, C., Caputo, S. L., Mazzotta, F., Trabattoni, D., Macias, J., Pineda, J. A., Caruz, A., & Clerici, M. (2013). Endoplasmic reticulum aminopeptidase 2 haplotypes play a role in modulating susceptibility to HIV infection. AIDS (London, England), 27(11), 1697-1706. https://doi.org/10.1097/QAD.0b013e3283601cee