Dipartimento di Scienze per la Promozione della Salute, Materno-Infantile di Medicina Interna e Specialistica di Eccellenza "G. D'Alessandro", 90133 Palermo, Italy.
Viruses. 2020 Nov 28;12(12):1363. doi: 10.3390/v12121363.
Therapies for HCV care could change the prevalence and the geographic distribution of genotypes due to differences in Sustained Virologic Response (SVR). In this scenario, uncommon genotypes/subtypes, such as genotype 4, could spread from high-risk groups, replacing genotypes eradicated by antiviral drugs. Genotype eradication is also strongly influenced by the CD8+ T cell response. In this study, the genetic variability in HCV genotype 4 strains obtained from a cohort of 67 patients naïve to DAA therapy was evaluated. We found that the presence of resistance-associated substitutions (RAS) was able to affect drug responses. Next, using a prediction tool, viral mutations were identified by their ability, or lack thereof, to reduce the binding affinity with HLA, which affects T cell recognition. The Bayesian coalescent analysis suggested two different circulation clusters, one in risk groups (IDUs and MSM) and the other due to migration flows, dated to 1940 and 1915, respectively. Most of the RAS overlapped with HLA and a lack of binding mutations was observed in 96% of strains. This study describes the introduction of HCV genotype 4 in a region of the Mediterranean basin and evaluates how HCV genotype 4's genetic variability could affect the response of antiviral drugs and CD8+ T cell recognition.
HCV 治疗方法可能会因持续病毒学应答 (SVR) 的差异而改变基因型的流行和地理分布。在这种情况下，不常见的基因型/亚型，如基因型 4，可能会从高风险群体中传播，取代被抗病毒药物根除的基因型。基因型的根除也受到 CD8+T 细胞反应的强烈影响。在这项研究中，评估了来自 67 名未接受 DAA 治疗的患者队列中获得的 HCV 基因型 4 株的遗传变异性。我们发现，耐药相关取代 (RAS) 的存在能够影响药物反应。接下来，使用预测工具，根据其降低与 HLA 结合亲和力的能力或缺乏能力来识别病毒突变，这会影响 T 细胞识别。贝叶斯凝聚分析表明存在两个不同的循环簇，一个在高危人群（IDU 和 MSW）中，另一个由于移民流动，分别可追溯到 1940 年和 1915 年。大多数 RAS 与 HLA 重叠，96%的菌株中观察到缺乏结合突变。本研究描述了 HCV 基因型 4 在地中海盆地地区的引入情况，并评估了 HCV 基因型 4 的遗传变异性如何影响抗病毒药物和 CD8+T 细胞识别的反应。
