Sherman K E, Andreatta C, O'Brien J, Gutierrez A, Harris R
Department of Medicine and Pathology, University of Cincinnati Medical Center, OH, USA.
Hepatology. 1996 Apr;23(4):688-94. doi: 10.1002/hep.510230405.
Patients coinfected with the hepatitis C virus (HCV) and the human immunodeficiency virus (HIV) were studied with regard to nucleotide sequence variability in the E2/NS1 first hypervariable region of the HCV genome. The nucleotide variability within individual patients was compared to patients infected only with HCV. The proportion of predicted synonymous and nonsynonymous amino acid changes, and the relationship to putative high-antigenicity sites, were evaluated in the hypervariable envelope domain. Ninety-one clones from 10 patients with HCV/HIV coinfection were sequenced, following polymerase chain reaction (PCR) amplification of the hypervariable region. The control HCV group included 53 clones from 7 patients. Sequence analysis encompassed the region coding for amino acids 384 to 414. Consensus sequences from each patient were used as the internal standard for nonsynonymous amino acid codon variability. Cumulative proportional comparison at each amino acid site revealed increased variability in HCV RNA from patients with HCV/HIV coinfection versus HCV alone (P < .05). The greatest variability was observed at amino acids 386, 397, 400, 402, 405, 407, and 414, with >l0 percent clonal variation at these sites. Jameson-Wolf plots were used to predict putative high-antigenicity domains. Nonsynonymous clonal variation resulted in alteration of putative antigenic sites within the hypervariable region. All clones had at least one high-probability site. Clones with unique predicted antigenic domains were observed more frequently in HIV/HCV coinfected patients, and, independent of viral titer, were consistent with increased sequence variability. These data suggest an accumulation of envelope variants in the HCV/HIV coinfected patients, which could be related to ineffective viral clearance, and may help explain prior reports of interferon (IFN) resistance in this patient group.
对丙型肝炎病毒（HCV）和人类免疫缺陷病毒（HIV）合并感染患者的HCV基因组E2/NS1第一高变区的核苷酸序列变异性进行了研究。将个体患者体内的核苷酸变异性与仅感染HCV的患者进行了比较。在高变包膜结构域中评估了预测的同义氨基酸和非同义氨基酸变化的比例，以及与假定的高抗原性位点的关系。在对高变区进行聚合酶链反应（PCR）扩增后，对10例HCV/HIV合并感染患者的91个克隆进行了测序。对照HCV组包括7例患者的53个克隆。序列分析涵盖了编码氨基酸384至414的区域。将每位患者的共有序列用作非同义氨基酸密码子变异性的内部标准。在每个氨基酸位点的累积比例比较显示，与单独感染HCV的患者相比，HCV/HIV合并感染患者的HCV RNA变异性增加（P <.05）。在氨基酸386、397、400、402、405、407和414处观察到最大变异性，这些位点的克隆变异率>10%。使用詹姆森-沃尔夫图预测假定的高抗原性结构域。非同义克隆变异导致高变区内假定抗原位点的改变。所有克隆至少有一个高概率位点。在HIV/HCV合并感染患者中更频繁地观察到具有独特预测抗原结构域的克隆，并且与病毒滴度无关，这与序列变异性增加一致。这些数据表明，HCV/HIV合并感染患者中包膜变体的积累可能与病毒清除无效有关，并且可能有助于解释该患者组先前关于干扰素（IFN）耐药性的报道。
