PMID- 23435305
OWN - NLM
STAT- MEDLINE
DCOM- 20140110
LR  - 20130627
IS  - 1473-5571 (Electronic)
IS  - 0269-9370 (Linking)
VI  - 27
IP  - 11
DP  - 2013 Jul 17
TI  - Endoplasmic reticulum aminopeptidase 2 haplotypes play a role in modulating 
      susceptibility to HIV infection.
PG  - 1697-706
LID - 10.1097/QAD.0b013e3283601cee [doi]
AB  - 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 x 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. CONCLUSION: ERAP2 hapA is correlated with resistance to HIV-1 
      infection, possibly secondarily to its effect on antigen processing and 
      presentation.
FAU - Biasin, Mara
AU  - Biasin M
AD  - Department of Biomedical and Clinical Sciences, University of Milan, Milan, 
      Italy. mara.biasin@unimi.it
FAU - Sironi, Manuela
AU  - Sironi M
FAU - Saulle, Irma
AU  - Saulle I
FAU - de Luca, Mariacristina
AU  - de Luca M
FAU - la Rosa, Francesca
AU  - la Rosa F
FAU - Cagliani, Rachele
AU  - Cagliani R
FAU - Forni, Diego
AU  - Forni D
FAU - Agliardi, Cristina
AU  - Agliardi C
FAU - lo Caputo, Sergio
AU  - lo Caputo S
FAU - Mazzotta, Francesco
AU  - Mazzotta F
FAU - Trabattoni, Daria
AU  - Trabattoni D
FAU - Macias, Juan
AU  - Macias J
FAU - Pineda, Juan A
AU  - Pineda JA
FAU - Caruz, Antonio
AU  - Caruz A
FAU - Clerici, Mario
AU  - Clerici M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - AIDS
JT  - AIDS (London, England)
JID - 8710219
RN  - 0 (HIV Core Protein p24)
RN  - 0 (HLA-B Antigens)
RN  - EC 3.4.11.- (Aminopeptidases)
RN  - EC 3.4.11.- (ERAP2 protein, human)
SB  - IM
MH  - Aminopeptidases/*genetics
MH  - *Disease Resistance
MH  - Enzyme-Linked Immunosorbent Assay
MH  - HIV Core Protein p24/biosynthesis
MH  - HIV Infections/*genetics
MH  - HIV-1/genetics/growth & development
MH  - HLA-B Antigens/genetics
MH  - Haplotypes
MH  - Humans
MH  - Italy
MH  - Male
MH  - Polymerase Chain Reaction
MH  - *Polymorphism, Single Nucleotide
MH  - Spain
EDAT- 2013/02/26 06:00
MHDA- 2014/01/11 06:00
CRDT- 2013/02/26 06:00
PHST- 2013/02/26 06:00 [entrez]
PHST- 2013/02/26 06:00 [pubmed]
PHST- 2014/01/11 06:00 [medline]
AID - 10.1097/QAD.0b013e3283601cee [doi]
PST - ppublish
SO  - AIDS. 2013 Jul 17;27(11):1697-706. doi: 10.1097/QAD.0b013e3283601cee.