Abbate Isabella, Lo Iacono Oreste, Di Stefano Rosa, Cappiello Giuseppina, Girardi Enrico, Longo Roberta, Ferraro Donatella, Antonucci Giorgio, Di Marco Vito, Solmone Mariacarmela, Craxì Antonio, Ippolito Giuseppe, Capobianchi Maria R
Department of Virology, National Institute for Infectious Diseases L. Spallanzani, Rome, Italy.
J Hepatol. 2004 May;40(5):831-6. doi: 10.1016/j.jhep.2004.01.019.
BACKGROUND/AIMS: HVR-1 quasispecies composition and evolution were investigated in patients chronically infected with genotype 1b HCV, treated with PEG-IFN alpha 2b or STD-IFN alpha 2b plus RBV.
HVR-1 heterogeneity was assessed by calculating nucleotidic complexity, diversity, synonymous (S) and non-synonymous (NS) substitutions at baseline, after 4 weeks of therapy (T1) and at follow-up (T18). Evolution of viral quasispecies was analysed by constructing phylogenetic trees.
No correlation of baseline viremia with heterogeneity was observed. Nucleotidic complexity was lower in patients showing early virological response, and tended to be inversely correlated to viral load decline at 4 weeks of treatment. In the majority of SR, profound changes of quasispecies composition occurred during 4 weeks of treatment, while in NR virtually no major changes of pre-therapy variants were observed. Relapse showed both patterns of quasispecies evolution. Virus quasispecies after follow-up was similar to that found at T1 in both Relapsers and NR patients.
Baseline parameters of HVR-1 heterogeneity seem to be involved in the early response to treatment, and early response is associated with profound variations in the HVR-1 quasispecies. Viral quasispecies surviving early therapeutic pressure are most likely able to give rise to either virus rebound or persistence at T18.
背景/目的：研究了聚乙二醇干扰素α-2b或标准干扰素α-2b联合利巴韦林治疗的1b型丙型肝炎病毒慢性感染患者的高变区1（HVR-1）准种组成及进化情况。
通过计算核苷酸复杂度、多样性、同义（S）和非同义（NS）替换来评估基线、治疗4周后（T1）及随访时（T18）的HVR-1异质性。通过构建系统发育树分析病毒准种的进化。
未观察到基线病毒血症与异质性之间的相关性。出现早期病毒学应答的患者核苷酸复杂度较低，且在治疗4周时与病毒载量下降呈负相关趋势。在大多数治疗成功（SR）患者中，治疗4周期间准种组成发生了深刻变化，而在治疗无反应（NR）患者中，治疗前变体几乎未发生重大变化。复发患者表现出两种准种进化模式。随访后的病毒准种在复发患者和NR患者中均与T1时相似。
HVR-1异质性的基线参数似乎参与了对治疗的早期反应，且早期反应与HVR-1准种的深刻变化相关。在早期治疗压力下存活的病毒准种很可能在T18时导致病毒反弹或持续存在。
