Perales Celia, Beach Nathan M, Sheldon Julie, Domingo Esteban
Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Campus de Cantoblanco, 28049 Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 08036 Barcelona, Spain.
Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Campus de Cantoblanco, 28049 Madrid, Spain.
Curr Opin Virol. 2014 Oct;8:38-44. doi: 10.1016/j.coviro.2014.05.003. Epub 2014 Jun 23.
Resistance to interferon (IFN) in hepatitis C virus (HCV) differs from resistance to standard, directly-acting antiviral (DAA) agents in that the virus confronts a multicomponent antiviral state evoked by IFN. This renders unlikely the repeated selection of the same specific mutations that confer an IFN-resistance phenotype. Comparison of amino acid sequences of viral proteins in HCV that replicates in the presence of IFN in vivo or in cell culture (with entire virus or subgenomic replicons) reveals very few common candidate IFN resistance substitutions. Multiple host and viral factors contribute to divergent responses to IFN. The environmental heterogeneity in which exogenous IFN is expected to exert its selective effect may increase as a result of incorporation of new DAAs in therapy.
丙型肝炎病毒（HCV）对干扰素（IFN）的耐药性与对标准直接作用抗病毒药物（DAA）的耐药性不同，因为该病毒面临着由IFN引发的多组分抗病毒状态。这使得不太可能反复选择赋予IFN耐药表型的相同特定突变。对在体内或细胞培养中（使用完整病毒或亚基因组复制子）在IFN存在下复制的HCV中病毒蛋白的氨基酸序列进行比较，发现很少有共同的候选IFN耐药性替代位点。多种宿主和病毒因素导致对IFN的不同反应。由于新的DAA药物被纳入治疗，预计外源性IFN发挥其选择作用的环境异质性可能会增加。
