Deep-sequencing of viral genomes from treatment-naive HIV-infected persons shows positive association between intrahost genetic diversity and viral load

Background: Infection with human immunodeficiency virus type 1 (HIV) typically results from transmission of a small and genetically uniform viral population. Following transmission, the virus population becomes more diverse because of recombination and acquired mutations through genetic drift and selection. Viral intrahost genetic diversity remains a major obstacle to the cure of HIV; however, there is a disagreement whether intrahost viral genetic diversification associates positively or negatively with disease progression and progression markers. Viral load is a key progression marker and understanding its relationship to viral intrahost genetic diversity could help design future strategies for HIV monitoring and treatment. Methods: We analyzed deep-sequenced viral genomes from 2,650 treatment-naive HIV-infected persons to measure the intrahost genetic diversity of 2,447 genomic codon positions as calculated by Shannon entropy. We tested for associations between viral load (VL) and am...研究背景：1型人类免疫缺陷病毒（human immunodeficiency virus type 1, HIV）感染通常由小规模且遗传均一的病毒种群传播引发。感染后，病毒种群因重组、遗传漂变与选择介导的获得性突变而逐渐变得更为多样。病毒的宿主内遗传多样性仍是艾滋病治愈的一大核心阻碍，但目前学界对于宿主内病毒遗传多样化与疾病进展及进展标志物之间呈正相关还是负相关仍存在争议。病毒载量是关键的疾病进展标志物，明确其与病毒宿主内遗传多样性的关联，可为未来艾滋病监测与治疗策略的制定提供参考依据。 研究方法：我们对2650名未经抗逆转录病毒治疗的HIV感染者的深度测序病毒基因组进行分析，以香农熵（Shannon entropy）为计算方法，对2447个基因组密码子位点的宿主内遗传多样性进行量化。我们检验了病毒载量（viral load, VL）与……之间的关联。