Moreau Isabelle, Hegarty Susan, Levis John, Sheehy Patrick, Crosbie Orla, Kenny-Walsh Elizabeth, Fanning Liam J
Molecular Virology Diagnostic & Research Laboratory, Department of Medicine, Clinical Sciences Building, Cork University Hospital, Cork, Ireland.
Virol J. 2006 Nov 15;3:95. doi: 10.1186/1743-422X-3-95.
Recombination between hepatitis C single stranded RNA viruses is a rare event. Natural viable intragenotypic and intergenotypic recombinants between 1b-1a, 1a-1c and 2k-1b, 2i-6p, respectively, have been reported. Diagnostically recombinants represent an intriguing challenge. Hepatitis C genotype is defined by interrogation of the sequence composition of the 5' untranslated region [5'UTR]. Occasionally, ambiguous specimens require further investigation of the genome, usually by interrogation of the NS5B region. The original purpose of this study was to confirm the existence of a suspected mixed genotype infection of genotypes 2 and 4 by clonal analysis at the NS5B region of the genome in two specimens from two separate individuals. This initial identification of genotype was based on analysis of the 5'UTR of the genome by reverse line probe hybridisation [RLPH].
The original diagnosis of a mixed genotype infection was not confirmed by clonal analysis of the NS5B region of the genome. The phylogenetic analysis indicated that both specimens were natural intergenotypic recombinant forms of HCV. The recombination was between genotypes 2k and 1b for both specimens. The recombination break point was identified as occurring within the NS2 region of the genome.
The viral recombinants identified here resemble the recombinant form originally identified in Russia. The RLPH pattern observed in this study may be a signature indicative of this particular type of intergenotype recombinant of hepatitis C meriting clonal analysis of NS2.
丙型肝炎单链RNA病毒之间的重组是一种罕见事件。分别在1b - 1a、1a - 1c以及2k - 1b、2i - 6p之间报道过自然存在的可行的基因内型和基因间型重组体。在诊断方面,重组体带来了一个有趣的挑战。丙型肝炎基因型是通过对5'非翻译区[5'UTR]的序列组成进行分析来定义的。偶尔,模糊的样本需要对基因组进行进一步研究,通常是通过对NS5B区域进行分析。本研究的最初目的是通过对来自两个不同个体的两个样本的基因组NS5B区域进行克隆分析,来确认2型和4型混合基因型感染的存在。这种基因型的初步鉴定是基于通过反向线探针杂交[RLPH]对基因组5'UTR的分析。
通过对基因组NS5B区域的克隆分析,未证实最初诊断的混合基因型感染。系统发育分析表明,两个样本都是丙型肝炎病毒的自然基因间型重组形式。两个样本的重组均发生在2k型和1b型之间。重组断点被确定发生在基因组的NS2区域内。
此处鉴定出的病毒重组体类似于最初在俄罗斯鉴定出的重组形式。本研究中观察到的RLPH模式可能是一种特征,表明这种特定类型的丙型肝炎基因间型重组体值得对NS2进行克隆分析。