Academic Journal
Virological and Immunological Factors Associated with HIV-1 Differential Disease Progression in HLA-B*58:01-Positive Individuals
| العنوان: | Virological and Immunological Factors Associated with HIV-1 Differential Disease Progression in HLA-B*58:01-Positive Individuals |
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| المؤلفون: | Chopera, D. R., Mlotshwa, M., Woodman, Z., Mlisana, K., de Assis Rosa, D., Martin, D. P., Abdool Karim, S., Gray, C. M., Williamson, C. |
| المصدر: | Journal of Virology ; volume 85, issue 14, page 7070-7080 ; ISSN 0022-538X 1098-5514 |
| بيانات النشر: | American Society for Microbiology |
| سنة النشر: | 2011 |
| الوصف: | Molecular epidemiology studies have identified HLA-B*58:01 as a protective HIV allele. However, not all B*58:01-expressing persons exhibit slow HIV disease progression. We followed six HLA-B*58:01-positive, HIV subtype C-infected individuals for up to 31 months from the onset of infection and observed substantial variability in their clinical progression despite comparable total breadths of T cell responses. We therefore investigated additional immunological and virological factors that could explain their different disease trajectories. Cytotoxic T-lymphocyte (CTL) responses during acute infection predominantly targeted the TW10 and KF9 epitopes in p24 Gag and Nef, respectively. Failure to target the TW10 epitope in one B*58:01-positive individual was associated with low CD4 + counts and rapid disease progression. Among those targeting TW10, escape mutations arose within 2 to 15 weeks of infection. Rapid escape was associated with preexisting compensatory mutations in the transmitted viruses, which were present at a high frequency (69%) in the study population. At 1 year postinfection, B*58:01-positive individuals who targeted and developed escape mutations in the TW10 epitope ( n = 5) retained significantly higher CD4 + counts ( P = 0.04), but not lower viral loads, than non-B*58:01-positive individuals ( n = 17). The high population-level frequency of these compensatory mutations may be limiting the protective effect of the B*58:01 allele. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1128/jvi.02543-10 |
| DOI: | 10.1128/JVI.02543-10 |
| الاتاحة: | http://dx.doi.org/10.1128/jvi.02543-10 https://journals.asm.org/doi/pdf/10.1128/JVI.02543-10 |
| Rights: | https://journals.asm.org/non-commercial-tdm-license |
| رقم الانضمام: | edsbas.11B87A1A |
| قاعدة البيانات: | BASE |
| DOI: | 10.1128/jvi.02543-10 |
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