Wiśniewski Janusz, Więcek Kamil, Ali Haider, Pyrc Krzysztof, Kula-Păcurar Anna, Wagner Marek, Chen Heng-Chang
Quantitative Virology Research Group, Population Diagnostics Center, Łukasiewicz Research Network - PORT Polish Center for Technology Development, Stabłowicka 147, 54-066 Wrocław, Poland.
Molecular Virology Group, Małopolska Centre of Biotechnology, Jagiellonian University, Gronostajowa 7A str, 30-387 Kraków, Poland.
iScience. 2024 Oct 21;27(11):111222. doi: 10.1016/j.isci.2024.111222. eCollection 2024 Nov 15.
HIV-1 reservoirs display a heterogeneous nature, lodging both intact and defective proviruses. To deepen our understanding of such heterogeneous HIV-1 reservoirs and their functional implications, we integrated basic concepts of graph theory to characterize the composition of HIV-1 reservoirs. Our analysis revealed noticeable topological properties in networks, featuring immunologic signatures enriched by genes harboring intact and defective proviruses, when comparing antiretroviral therapy (ART)-treated HIV-1-infected individuals and elite controllers. The key variable, the rich factor, played a pivotal role in classifying distinct topological properties in networks. The host gene expression strengthened the accuracy of classification between elite controllers and ART-treated patients. Markov chain modeling for the simulation of different graph networks demonstrated the presence of an intrinsic barrier between elite controllers and non-elite controllers. Overall, our work provides a prime example of leveraging genomic approaches alongside mathematical tools to unravel the complexities of HIV-1 reservoirs.
HIV-1储存库具有异质性，包含完整和缺陷型前病毒。为了加深我们对这种异质性HIV-1储存库及其功能影响的理解，我们整合了图论的基本概念来描述HIV-1储存库的组成。我们的分析揭示了网络中显著的拓扑特性，在比较接受抗逆转录病毒疗法（ART）治疗的HIV-1感染者和精英控制者时，具有完整和缺陷型前病毒的基因富集的免疫特征。关键变量——丰富因子，在区分网络中不同的拓扑特性方面发挥了关键作用。宿主基因表达提高了精英控制者和接受ART治疗患者之间分类的准确性。用于模拟不同图网络的马尔可夫链模型表明，精英控制者和非精英控制者之间存在内在障碍。总体而言，我们的工作提供了一个利用基因组方法和数学工具来揭示HIV-1储存库复杂性的典型例子。
