Mahmud Rizwan, Krullaars Zoë, van Osch Jolieke, Rickett David, Brumme Zabrina L, Hensley Kathryn S, Rokx Casper, Gruters Rob A, van Kampen Jeroen J A, Mesplède Thibault
Viroscience Department, Erasmus University Medical Center, 3015GD Rotterdam, The Netherlands.
British Columbia Centre for Excellence in HIV/AIDS, Vancouver, BC V6Z1Y6, Canada.
Pathogens. 2025 Feb 20;14(3):207. doi: 10.3390/pathogens14030207.
The presentation of HIV peptides by the human leukocyte antigen (HLA) complex to CD8+ cytotoxic T-cells (CTLs) is critical to limit viral pathogenesis. HIV can mutate to evade HLA-restricted CTL responses and resist antiretroviral drugs, raising questions about how it balances these evolutionary pressures. Here, we used a computational approach to assess how drug resistance-associated mutations (RAMs) affect the binding of HIV-1 subtype B or C peptides to the most prevalent HLA alleles in US, European, and South African populations. We predict RAMs that may be favored in certain populations and report the under-representation of Y181C in people expressing HLA-B*57:01. This finding agreed with our computational predictions when Y181C was at the major anchor site P2, suggesting the potential relevance of our approach. Overall, our findings lay out a conceptual framework to study the implications of HLA alleles on the emergence of HIV RAMs at the individual and population levels.
人类白细胞抗原（HLA）复合物将HIV肽呈递给CD8 + 细胞毒性T细胞（CTL）对于限制病毒发病机制至关重要。HIV可发生突变以逃避HLA限制的CTL反应并抵抗抗逆转录病毒药物，这引发了关于其如何平衡这些进化压力的问题。在这里，我们使用一种计算方法来评估耐药相关突变（RAM）如何影响HIV-1 B或C亚型肽与美国、欧洲和南非人群中最普遍的HLA等位基因的结合。我们预测了在某些人群中可能受到青睐的RAM，并报告了在表达HLA-B*57:01的人群中Y181C的代表性不足。当Y181C位于主要锚定位点P2时，这一发现与我们的计算预测一致，表明我们方法的潜在相关性。总体而言，我们的研究结果为在个体和人群水平上研究HLA等位基因对HIV RAM出现的影响奠定了概念框架。
