PMID- 20834103
OWN - NLM
STAT- MEDLINE
DCOM- 20101216
LR  - 20100913
IS  - 2040-2058 (Electronic)
IS  - 1359-6535 (Linking)
VI  - 15
IP  - 6
DP  - 2010
TI  - Analysis of immune selection as a potential cause for the presence of cleavage 
      site mutation 431V in treatment-naive HIV type-1 isolates.
PG  - 907-12
LID - 10.3851/IMP1640 [doi]
AB  - INTRODUCTION: HIV type-1 (HIV-1) protease (PR) and cleavage site (CS) mutations 
      accumulate in protease-inhibitor-resistant isolates. HIV-1 CS mutation 431V is 
      the most frequent treatment-associated CS mutation; however, little is known 
      about its origin in treatment-naive HIV-1 isolates. Recently, it has been shown 
      that the CS mutation 431V is located within the human leukocyte antigen 
      (HLA)-B*13-restricted cytotoxic T-lymphocyte (CTL) epitope RQANFLGKI (RI9). 
      Therefore, we investigated whether the presence of CS mutation 431V might 
      additionally be related to immune escape. METHODS: CTL recognition of RI9 and of 
      RI9 variants carrying the 431V or the 436R mutation was analysed by ELISPOT in 
      nine HLA-B*13-positive HIV-1-infected patients. Treatment-naive HIV-1-infected 
      patients with primary drug-resistant HIV-1 isolates (n=58) or carrying 431V (n=4) 
      were genotyped for HLA class I alleles. RESULTS: ELISPOT analysis showed 
      different patterns of CTL recognition of RI9. CS mutation 431V could abrogate 
      recognition by RI9-specific CTL in a subgroup of patients. Nevertheless, in our 
      study, the occurrence of 431V in treatment-naive HIV-1 without primary drug 
      resistance could not be explained by HLA-B*13-mediated immune selection. In 
      patients with primary drug-resistant HIV-1 isolates, the frequency of HLA-B*13 
      was not increased and HLA-B*13 did not correlate with CS mutations 436R or 431V. 
      CONCLUSIONS: HIV-1 CS mutation 431V can abrogate CTL recognition, indicating 
      interactions between development of drug resistance and the CTL response. 
      However, we could not find evidence that the presence of 431V in treatment-naive 
      HIV-1 isolates with and without primary drug resistance is related to immune 
      selection by HLA-B*13 or other HLA class I alleles.
FAU - Verheyen, Jens
AU  - Verheyen J
AD  - Institute of Virology, University of Cologne, Germany. jens.verheyen@uk-koeln.de
FAU - Schweitzer, Finja
AU  - Schweitzer F
FAU - Harrer, Ellen G
AU  - Harrer EG
FAU - Knops, Elena
AU  - Knops E
FAU - Mueller, Sandra M
AU  - Mueller SM
FAU - Daumer, Martin
AU  - Daumer M
FAU - Eismann, Kathrin
AU  - Eismann K
FAU - Bergmann, Silke
AU  - Bergmann S
FAU - Spriewald, Bernd M
AU  - Spriewald BM
FAU - Kaiser, Rolf
AU  - Kaiser R
FAU - Harrer, Thomas
AU  - Harrer T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Antivir Ther
JT  - Antiviral therapy
JID - 9815705
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (HLA-B Antigens)
RN  - 0 (Protease Inhibitors)
RN  - 0 (gag Gene Products, Human Immunodeficiency Virus)
SB  - IM
MH  - Case-Control Studies
MH  - Cohort Studies
MH  - Drug Resistance, Multiple, Viral
MH  - Epitopes, T-Lymphocyte/genetics/immunology
MH  - HIV Infections/*immunology
MH  - HIV-1/*genetics/immunology/isolation & purification
MH  - HLA-B Antigens/immunology
MH  - Humans
MH  - *Mutation
MH  - Protease Inhibitors/therapeutic use
MH  - T-Lymphocytes, Cytotoxic/*immunology/virology
MH  - gag Gene Products, Human Immunodeficiency Virus/immunology
EDAT- 2010/09/14 06:00
MHDA- 2010/12/17 06:00
CRDT- 2010/09/14 06:00
PHST- 2010/09/14 06:00 [entrez]
PHST- 2010/09/14 06:00 [pubmed]
PHST- 2010/12/17 06:00 [medline]
AID - 10.3851/IMP1640 [doi]
PST - ppublish
SO  - Antivir Ther. 2010;15(6):907-12. doi: 10.3851/IMP1640.