Torres-Puente Manuela, Cuevas José M, Jiménez-Hernández Nuria, Bracho María A, García-Robles Inmaculada, Carnicer Fernando, del Olmo Juan, Ortega Enrique, Moya Andrés, González-Candelas Fernando
Instituto Cavanilles de Biodiversidad y Biología Evolutiva and Departamento de Genética, Universidad de Valencia, Valencia, Spain.
J Med Virol. 2008 Feb;80(2):247-53. doi: 10.1002/jmv.21060.
The degree of variability of the interferon sensitivity determining region (ISDR) in the hepatitis C virus (HCV) genome has been postulated to predict the response to interferon therapy, mainly in patients infected with subtype 1b, although this prediction has been the subject of a long controversy. This prediction has been tested by analyzing a cohort of 67 Spanish patients infected with HCV genotype 1, 23 of which were infected with subtype 1a and 44 with subtype 1b. A sample previous to therapy with alpha-interferon plus ribavirin was obtained and several clones (between 25 and 96) including the ISDR were sequenced from each patient. A significant correlation between mutations at the ISDR and response to treatment for subtype 1b patients, but not for those infected with subtype 1a, has been detected. Although the results suggest that the same relationship holds true for subtype 1a, lack of statistical power because of the small sample size of this subtype prevented firmer conclusions. However, identical ISDR sequences were found in responder and non-responder patients, suggesting that the stability of the ISDR sequence can occasionally help HCV to evade interferon therapy, although this is not a sufficient condition. More complex interactions, including the ISDR or not, are likely to exist and govern the HCV response to interferon treatment.
丙型肝炎病毒（HCV）基因组中干扰素敏感性决定区（ISDR）的变异程度已被假定用于预测干扰素治疗的反应，主要是在感染1b亚型的患者中，尽管这一预测一直存在长期争议。通过分析一组67名感染HCV 1型的西班牙患者对这一预测进行了检验，其中23名感染1a亚型，44名感染1b亚型。获取了使用α干扰素加利巴韦林治疗前的样本，并对每位患者的包括ISDR在内的若干克隆（25至96个）进行了测序。已检测到ISDR处的突变与1b亚型患者的治疗反应之间存在显著相关性，但感染1a亚型的患者则不然。尽管结果表明1a亚型也存在相同的关系，但由于该亚型样本量小而缺乏统计学效力，无法得出更确凿的结论。然而，在有反应和无反应的患者中发现了相同的ISDR序列，这表明ISDR序列的稳定性偶尔可能有助于HCV逃避干扰素治疗，尽管这不是一个充分条件。可能存在包括ISDR与否在内的更复杂的相互作用，并决定HCV对干扰素治疗的反应。
