Leung Preston, Bull Rowena, Lloyd Andrew, Luciani Fabio
Inflammation and Infection Research Centre, School of Medical Sciences, The University of New South Wales, Sydney, NSW 2052, Australia.
Biomed Res Int. 2014;2014:264519. doi: 10.1155/2014/264519. Epub 2014 Jun 10.
Rapidly mutating viruses, such as hepatitis C virus (HCV) and HIV, have adopted evolutionary strategies that allow escape from the host immune response via genomic mutations. Recent advances in high-throughput sequencing are reshaping the field of immuno-virology of viral infections, as these allow fast and cheap generation of genomic data. However, due to the large volumes of data generated, a thorough understanding of the biological and immunological significance of such information is often difficult. This paper proposes a pipeline that allows visualization and statistical analysis of viral mutations that are associated with immune escape. Taking next generation sequencing data from longitudinal analysis of HCV viral genomes during a single HCV infection, along with antigen specific T-cell responses detected from the same subject, we demonstrate the applicability of these tools in the context of primary HCV infection. We provide a statistical and visual explanation of the relationship between cooccurring mutations on the viral genome and the parallel adaptive immune response against HCV.
快速变异的病毒,如丙型肝炎病毒(HCV)和人类免疫缺陷病毒(HIV),采取了进化策略,通过基因组突变逃避宿主免疫反应。高通量测序的最新进展正在重塑病毒感染免疫病毒学领域,因为这些技术能够快速且廉价地生成基因组数据。然而,由于产生的数据量巨大,全面理解此类信息的生物学和免疫学意义往往很困难。本文提出了一种流程,可对与免疫逃逸相关的病毒突变进行可视化和统计分析。利用来自单一HCV感染期间HCV病毒基因组纵向分析的下一代测序数据,以及从同一受试者检测到的抗原特异性T细胞反应,我们证明了这些工具在原发性HCV感染背景下的适用性。我们对病毒基因组上同时发生的突变与针对HCV的平行适应性免疫反应之间的关系进行了统计和可视化解释。