Artikel
Correlations between transmitted HIV-1 drug resistance mutations and the HLA alleles of therapy-naïve HIV-patients
Korrelationen zwischen übertragenen HIV-1 Resistenzmutationen und den HLA Allelen von therapie-naiven HIV Patienten
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Autoren
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F. Schweitzer
- Universität zu Köln, Germany
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S. Müller
- Universität Erlangen-Nürnberg, Erlangen, Germany
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M. Däumer
- Institut für Immunologie und Genetik, Kaiserslautern, Germany
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R. Kaiser
- Universität zu Köln, Germany
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M. Oette
- Krankenhaus der Augustinerinnen, Köln, Germany
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T. Lengauer
- Max Planck Institut für Informatik, Köln, Germany
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T. Harrer
- Universität Erlangen-Nürnberg, Erlangen, Germany
| Veröffentlicht: | 2. Juni 2010 |
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Gliederung
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Background: ART of HIV-1 infected patients is successful but limited due to occurrences of drug resistances mutations. In therapy-naïve patients the immune system is the main force selecting mutations allowing the virus to escape recognition by CTLs. We hypothesize that these CTL specific mutations can influence the persistence of transmitted resistance mutations. Our data indicate correlations between transmitted resistance mutations and HLA-types of RESINA patients.
Methods: Using the programs SYFPEITHI and ELF we analyzed if the detected resistance mutations are located in putative CTL epitopes. With the help of enzyme-linked immunospot technique (ELISPOT) assays we investigated the recognition of these assumed epitopes using peptide stimulated cell lines derived from a cohort of HLA-typed HIV-1-infected patients.
Results: Using Fisher's exact test several correlations between resistance mutations and HLA alleles were detected in patients of the RESINA study. Correlations were found between HLA-A*01 and the mutation L33F (PR), between HLA-A*03 and M46I (PR), between HLA-A*11 and V75I (RT) and between HLA-B*44 and L210F (RT) and K103R (RT), respectively. In ELISPOT analyses, peptides were indeed recognized by the cells of patients carrying the HLA allele which showed a statistical correlation to the respective resistance mutation, indicating that HLA-A*01, HLA-A*03 and HLA-A*11 epitopes are located in the designated regions.
More detailed analyses were conducted for L210F. ELISPOT assays using cells from HLA-B*44 positive RESINA patients revealed the L210F to be an immune escape mutation.
Conclusion: The HLA-system seems to play a role in the evolution of drug resistance mutations, even in therapy-naïve patients.
