丙型肝炎病毒遗传多样性可用于推断感染时间的新近程度和感染时间。
HCV Genetic Diversity Can Be Used to Infer Infection Recency and Time since Infection.
机构信息
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, CH-8091 Zurich, Switzerland.
Institute of Medical Virology, University of Zurich, CH-8057 Zurich, Switzerland.
出版信息
Viruses. 2020 Oct 31;12(11):1241. doi: 10.3390/v12111241.
HIV-1 genetic diversity can be used to infer time since infection (TSI) and infection recency. We adapted this approach for HCV and identified genomic regions with informative diversity. We included 72 HCV/HIV-1 coinfected participants of the Swiss HIV Cohort Study, for whom reliable estimates of infection date and viral sequences were available. Average pairwise diversity (APD) was calculated over each codon position for the entire open reading frame of HCV. Utilizing cross validation, we evaluated the correlation of APD with TSI, and its ability to infer TSI via a linear model. We additionally studied the ability of diversity to classify infections as recent (infected for <1 year) or chronic, using receiver-operator-characteristic area under the curve (ROC-AUC) in 50 patients whose infection could be unambiguously classified as either recent or chronic. Measuring HCV diversity over third or all codon positions gave similar performances, and notable improvement over first or second codon positions. APD calculated over the entire genome enabled classification of infection recency (ROC-AUC = 0.76). Additionally, APD correlated with TSI (R = 0.33) and could predict TSI (mean absolute error = 1.67 years). Restricting the region over which APD was calculated to - further improved accuracy (ROC-AUC = 0.85, R = 0.54, mean absolute error = 1.38 years) Genetic diversity in HCV correlates with TSI and is a proxy for infection recency and TSI, even several years post-infection.
HIV-1 基因多样性可用于推断感染时间(TSI)和感染近期情况。我们将这种方法应用于 HCV,并确定了具有信息多样性的基因组区域。我们纳入了 72 名瑞士艾滋病毒队列研究中的 HCV/HIV-1 合并感染参与者,这些参与者的感染日期和病毒序列都有可靠的估计。计算 HCV 整个开放阅读框中每个密码子位置的平均成对多样性(APD)。利用交叉验证,我们评估了 APD 与 TSI 的相关性,以及通过线性模型推断 TSI 的能力。我们还在 50 名患者中研究了多样性分类感染为近期(感染<1 年)或慢性的能力,使用 50 名患者的接受者操作特征曲线下面积(ROC-AUC)来明确分类近期或慢性感染。测量 HCV 第三或所有密码子位置的多样性会产生相似的性能,并且比第一或第二密码子位置有明显的提高。在整个基因组上计算 APD 可以对感染近期情况进行分类(ROC-AUC = 0.76)。此外,APD 与 TSI 相关(R = 0.33),并且可以预测 TSI(平均绝对误差= 1.67 年)。将 APD 计算的区域限制在 - 进一步提高了准确性(ROC-AUC = 0.85,R = 0.54,平均绝对误差= 1.38 年)。HCV 的遗传多样性与 TSI 相关,是感染近期情况和 TSI 的替代指标,即使在感染后几年也是如此。