Department of Virology, Tarbiat Modares University, Tehran, Iran.
J Med Virol. 2011 Aug;83(8):1332-7. doi: 10.1002/jmv.22144.
Heterogeneity of subgenomic regions of hepatitis C virus (HCV) may be associated with response to interferon (IFN) therapy. The amino acid sequences of the PKR/eIF-2α phosphorylation homology domain (pePHD), IFN sensitivity determining region (ISDR), PKR binding domain (PKRBD), and variable region 3 (V3) were studied in 19 patients before and after 4 weeks of treatment. All patients were infected with HCV genotype 1a and were treated with pegylated-IFN and ribavirin. Thirteen patients achieved sustained viral response (responders) and six failed to clear viral RNA (nonresponders). The amino acid sequences in the pePHD and ISDR were identical in responders and nonresponders. However, amino acid substitution at position 2252 of PKRBD was significantly different between responders and nonresponders (P = 0.044). A larger number of mutations were observed in the V3 region of responders (P < 0.001). In this region, the amino acid in position 2364 differed between responders and nonresponders (responders: aspartic acid and serine, nonresponders: asparagine, P = 0.018). The amino acid sequences in the regions which were studied did not change after 4 weeks of treatment. It is concluded that the presence of specific amino acids in position 2252 of PKRBD and position 2364 of V3 might be associated with clinical response to IFN.
丙型肝炎病毒（HCV）亚基因组区域的异质性可能与干扰素（IFN）治疗的反应有关。在 19 例接受聚乙二醇干扰素和利巴韦林治疗 4 周前后，研究了 PKR/eIF-2α磷酸化同源结构域（pePHD）、IFN 敏感性决定区（ISDR）、PKR 结合域（PKRBD）和可变区 3（V3）的氨基酸序列。所有患者均感染 HCV 基因型 1a，13 例患者获得持续病毒应答（应答者），6 例患者未能清除病毒 RNA（无应答者）。应答者和无应答者的 pePHD 和 ISDR 氨基酸序列相同。然而，PKRBD 位置 2252 的氨基酸取代在应答者和无应答者之间存在显著差异（P=0.044）。应答者的 V3 区观察到更多的突变（P<0.001）。在该区域，位置 2364 的氨基酸在应答者和无应答者之间存在差异（应答者：天冬氨酸和丝氨酸，无应答者：天冬酰胺，P=0.018）。在治疗 4 周后，研究区域的氨基酸序列没有改变。结论是 PKRBD 位置 2252 和 V3 位置 2364 特定氨基酸的存在可能与 IFN 的临床反应有关。
