Diverged Adaptation of Hepatitis C Virus Genotypes 1 and 3 to Human Leukocyte Antigen-Restricted Immune Pressure
Diverged Adaptation of Hepatitis C Virus Genotypes 1 and 3 to Human Leukocyte Antigen-Restricted Immune Pressure
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DOI：
10.1002/hep.23101
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发表时间：
2009-10-01
期刊：
影响因子：
13.5
通讯作者：
Gaudieri, Silvana
中科院分区：
文献类型：
--
作者：
Rauch, Andri;James, Ian;Gaudieri, Silvana
世界范围内的许多丙型肝炎病毒（HCV）感染都是基因型I和3株病毒。已知细胞免疫应答在HCV基因型I感染的遏制中是重要的，并且已经鉴定了由宿主人白细胞抗原（HLA）呈递的许多基因型I T细胞靶标（表位）。相比之下，几乎没有关于基因型3的等效响应的信息。HCV使用的免疫逃逸机制包括病毒多态性（适应性）的进化，其消除了这种宿主-病毒相互作用。HCV适应HI-A限制性免疫压力的证据可以在人群水平上观察到与特定HLA类型相关的病毒多态性。为了评估HCV基因型1和3的逃逸模式，我们评估了187名基因型la和136名基因型3a感染者的病毒多态性和特定HLA类型之间的相关性。我们鉴定了51个HILA相关的病毒多态性（32个为基因型Ia，19个为基因型3a）。在这些假定的病毒适应位点中，有6个属于先前发表的表位。只有两个HI-A相关的病毒多态性是共同的两种基因型。在其余的位点与HI-A相关的多态性，有完全的保守性或没有显着的HLA与病毒多态性的替代基因型。这项研究还强调了病毒逃避免疫反应的不同机制，以及基因型变异在这些过程中的作用。结论：两种基因型的HCV非结构蛋白的HI-A相关多态性几乎没有重叠，这意味着作用于这些病毒的细胞免疫压力和不同的逃逸模式存在差异。这些发现对未来对抗HCV感染的治疗策略，包括疫苗设计具有重要意义。（《肝脏病学》2009年;50：1017-1029。）
Many hepatitis C virus (HCV) infections worldwide are with the genotype I and 3 strains of the virus. Cellular immune responses are known to be important in the containment of HCV genotype I infection, and many genotype 1 T cell targets (epitopes) that are presented by host human leukocyte, antigens (HLAs) have been identified. In contrast, there is almost no information known about the equivalent responses to genotype 3. Immune escape mechanisms used by HCV include the evolution of viral polymorphisms (adaptations) that abrogate this host-viral interaction. Evidence of HCV adaptation to HI-A-restricted immune pressure on HCV can be observed at the population level as viral polymorphisms associated with specific HLA types. To evaluate the escape patterns of HCV genotypes 1 and 3, we assessed the associations between viral polymorphisms and specific HLA types from 187 individuals with genotype la and 136 individuals with genotype 3a infection. We identified 51 HILA-associated viral polymorphisms (32 for genotype la and 19 for genotype 3a). Of these putative viral adaptation sites, six fell within previously published epitopes. Only two HI-A-associated viral polymorphisms were common to both genotypes. In the remaining sites with HI-A-associated polymorphisms, there was either complete conservation or no significant HLA association with viral polymorphism in the alternative genotype. This study also highlights the diverse mechanisms by which viral evasion of immune responses may be achieved and the role of genotype variation in these processes. Conclusion: There is little overlap in HI-A-associated polymorphisms in the nonstructural proteins of HCV for the two genotypes, implying differences in the cellular immune pressures acting on these viruses and different escape profiles. These findings have implications for future therapeutic strategies to combat HCV infection, including vaccine design. (HEPATOLOGY 2009;50:1017-1029.)