Bukowska-Ośko Iwona, Caraballo Cortés Kamila, Pawełczyk Agnieszka, Płoski Rafał, Fic Maria, Perlejewski Karol, Demkow Urszula, Berak Hanna, Horban Andrzej, Laskus Tomasz, Radkowski Marek
Department of Immunopathology of Infectious and Parasitic Diseases, Medical University of Warsaw, 3c Pawińskiego Street, 02-106 Warsaw, Poland.
Department of Medical Genetics, Medical University of Warsaw, 3c Pawińskiego Street, 02-106 Warsaw, Poland.
Biomed Res Int. 2014;2014:175405. doi: 10.1155/2014/175405. Epub 2014 Jul 3.
Hepatitis C virus (HCV) highly conserved IRES (internal ribosome entry site) sequence, localized within the 5(')-untranslated region (5(')UTR), may determine viral properties like replication efficiency and cell tropism. The aim of the present study was to characterize newly emerging 5(')UTR variants in serum and peripheral blood mononuclear cells (PBMC) in chronic hepatitis C patients treated with interferon (IFN) and ribavirin and to identify their effect on IRES secondary structures. The study group consisted of 87 patients infected with genotype 1b from whom serum and PBMC samples were collected at 9 time points (before, during, and after treatment). New 5(')UTR variants developed in 9 patients. Out of the overall 14 new variants, 9 (64%) were found in PBMC. HCV variants with decreased thermodynamic stability were identified only in PBMC and C183U mutation was the most common one in this compartment. In conclusion, antiviral treatment may favor emergence of new 5(')UTR variants both in blood and in PBMC compartments. However, variants developing in the latter compartment were predicted to have lower thermodynamic stability of the IRES secondary structures compared to serum strains. C-U change in position 183, which has not been described previously, might indicate viral adaptation to lymphoid cells.
丙型肝炎病毒（HCV）高度保守的内部核糖体进入位点（IRES）序列位于5′非翻译区（5′UTR）内，可能决定病毒的特性，如复制效率和细胞嗜性。本研究的目的是对接受干扰素（IFN）和利巴韦林治疗的慢性丙型肝炎患者血清和外周血单核细胞（PBMC）中新出现的5′UTR变体进行特征分析，并确定它们对IRES二级结构的影响。研究组由87例感染1b基因型的患者组成，在9个时间点（治疗前、治疗期间和治疗后）采集他们的血清和PBMC样本。9例患者出现了新的5′UTR变体。在总共14个新变体中，9个（64%）在PBMC中被发现。仅在PBMC中鉴定出热力学稳定性降低的HCV变体，C183U突变是该区域最常见的变体。总之，抗病毒治疗可能有利于血液和PBMC区室中新的5′UTR变体的出现。然而，与血清毒株相比，在后一区室中出现的变体预计IRES二级结构的热力学稳定性较低。先前未描述的183位的C-U变化可能表明病毒对淋巴细胞的适应性。
