title: Endoplasmic reticulum aminopeptidase 2 haplotypes play a role in modulating susceptibility to HIV infection.
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. 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.
  
  
  CONCLUSIONS
  ERAP2 hapA is correlated with resistance to HIV-1 infection, possibly secondarily to its effect on antigen processing and presentation.
authors: Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy. mara.biasin@unimi.it
authors: Mara
authors: M
authors: Biasin
authors: Manuela
authors: M
authors: Sironi
authors: Irma
authors: I
authors: Saulle
authors: Mariacristina
authors: M
authors: de Luca
authors: Francesca
authors: F
authors: la Rosa
authors: Rachele
authors: R
authors: Cagliani
authors: Diego
authors: D
authors: Forni
authors: Cristina
authors: C
authors: Agliardi
authors: Sergio
authors: S
authors: lo Caputo
authors: Francesco
authors: F
authors: Mazzotta
authors: Daria
authors: D
authors: Trabattoni
authors: Juan
authors: J
authors: Macias
authors: Juan A
authors: JA
authors: Pineda
authors: Antonio
authors: A
authors: Caruz
authors: Mario
authors: M
authors: Clerici
mesh_terms: D000626:Aminopeptidases / Q000235:genetics*; D060467:Disease Resistance; D004797:Enzyme-Linked Immunosorbent Assay; D016655:HIV Core Protein p24 / Q000096:biosynthesis; D015658:HIV Infections / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics / Q000254:growth & development; D015235:HLA-B Antigens / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D007558:Italy; D008297:Male; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D013030:Spain
chemical_list: D016655:HIV Core Protein p24; D015235:HLA-B Antigens; D000626:Aminopeptidases; C503944:ERAP2 protein, human