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Displaying record number 54665

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HXB2 Location	Pol(112-122) Protease(56-66) DNA(2418..2450)	Pol Epitope Map
Author Location	Protease(56-66 HXB2)
Epitope	VRQYDQIPIEI	Epitope Alignment
Epitope Name	VI11
Subtype	B
Species (MHC/HLA)	human(B13)
Immunogen	HIV-1 infection
Country	Germany
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	escape, mutation acquisition, HLA associated polymorphism, drug resistance

Notes

• To assess HIV-1-specific CTL influence on development and patterns of drug resistance in protease (PR) 94 HLA-typed patients were analyzed. 10 new CTL epitopes were defined statistically and experimentally, and 26 correlations (positive and negative) between HLA class-I alleles and PR mutations - some leading to escape mutations - were detected, demonstrating that CTL epitopes can be predicted based on HLA-amino acid substitution associations.
• Some patient CTL escape mutations were detectable by other CTLs of the same patient. Correlations between resistance mutations, polymorphisms and specific PR inhibitors were not detected.
• HLA-B had the strongest impact on PR sequence change, though HLAs-A and -C also had some impact.
• The authors suggest that CTL escape is active in developing drug-resistance related polymorphisms as well as major and minor mutations in HIV-1 infected persons.
• HIV-1 subtype breakdown in this cohort was follows - 83/94 patients infected with subtype B virus, 3 with subtype C, 4 CRF01_AE, 1 CRF03_AB, 1 CRF15_01B and 2 subtype Ds.
• This newly defined HLA-B13-restricted epitope, VRQYDQIPIEI, VI11, carries drug-induced mutations I62V, VRQYDQvPIEI and E65D, VRQYDQIPIdI.
• VI11 epitope and variant peptides include the L63P substitution when compared to HXB2 strain sequences.

References

Mueller2007 Sandra M. Mueller, Birgit Schaetz, Kathrin Eismann, Silke Bergmann, Michael Bauerle, Matthias Schmitt-Haendle, Hauke Walter, Barbara Schmidt, Klaus Korn, Heinrich Sticht, Bernd Spriewald, Ellen G. Harrer, and Thomas Harrer. Dual Selection Pressure by Drugs and HLA Class I-Restricted Immune Responses on Human Immunodeficiency Virus Type 1 Protease. J. Virol., 81(6):2887-2898, Mar 2007. PubMed ID: 17202219. Show all entries for this paper.