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Displaying record number 54660

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HXB2 Location	Pol(118-126) Protease(62-70) DNA(2436..2462)	Pol Epitope Map
Author Location	Protease(62-70 HXB2)
Epitope	ILIEICGHK	Epitope Alignment
Epitope Name	IK9
Subtype	B
Species (MHC/HLA)	human(A3)
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 epitope, ILIEICGHK, IK9, has a variant K70R, ILIEICGHr, which strongly reduced recognition by CTL as it is a C-terminal anchor site. Also the minor mutation I64V, ILvEICGHK, is negatively associated with HLA-A3, indicating that it rarely occurs in A3-patients.

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.