Park Vicki M, Mason Barbara C, Krushkal Julia, Li Rongling, Riely Caroline, Fleckenstein Jaquelyn
Department of Pediatrics, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA.
Dig Dis Sci. 2007 Oct;52(10):2540-9. doi: 10.1007/s10620-006-9726-8. Epub 2007 Apr 5.
In a prospective therapeutic trial, features of the hepatitis C quasispecies were investigated as possible markers of therapeutic response. Individuals chronically infected with hepatitis C genotype 1 received antiviral therapy consisting of alpha-interferon plus ribavirin. The study targeted the most rapidly evolving segment of the viral genome, hypervariable region 1 within the envelope-2 gene. Among individuals failing to clear virus in response to therapy, significant differences were observed between quasispecies of African-American and Caucasian subjects. While distance measures for synonymous substitutions were similar between racial subgroups, measures of distance at the amino acid level (nonsynonymous substitutions) varied significantly. Taken together, the observed patterns of variability corresponded to reduced host selection pressure against hypervariable region 1 in African-American nonresponders. Reduced selection pressure was present at baseline and persisted through treatment and follow-up, suggesting population stratification of host factors that influence selection pressure on hepatitis C virus.
在一项前瞻性治疗试验中，对丙型肝炎准种的特征进行了研究，以确定其是否可能作为治疗反应的标志物。慢性感染丙型肝炎基因1型的个体接受了由α干扰素加利巴韦林组成的抗病毒治疗。该研究针对病毒基因组中进化最快的部分，即包膜-2基因内的高变区1。在对治疗无反应而未能清除病毒的个体中，观察到非裔美国人和白种人受试者的准种之间存在显著差异。虽然种族亚组之间同义替换的距离测量相似，但氨基酸水平（非同义替换）的距离测量差异很大。综合来看，观察到的变异模式对应于非裔美国无反应者中针对高变区1的宿主选择压力降低。在基线时就存在选择压力降低的情况，并在治疗和随访过程中持续存在，这表明影响丙型肝炎病毒选择压力的宿主因素存在人群分层。
