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丙型肝炎病毒变异体在从一名受感染供血者输血给多名受血者后的演变:长期随访

Evolution of hepatitis C virus variants following blood transfusion from one infected donor to several recipients: a long-term follow-up.

作者信息

Löve Arthur, Molnegren Vilma, Månsson Ann-Sofie, Smáradóttir Agnes, Thorsteinsson Sigurdur B, Widell Anders

机构信息

Department of Medical Virology, Landspitali-University Hospital, University of Iceland, Reykjavik, Iceland.

Department of Medical Microbiology, Malmö University Hospital, Lund University, SE-20502 Malmö, Sweden.

出版信息

J Gen Virol. 2004 Feb;85(Pt 2):441-450. doi: 10.1099/vir.0.19439-0.

DOI:10.1099/vir.0.19439-0
PMID:14769902
Abstract

Variants of hepatitis C virus (HCV) from a single infected blood donor and 13 viraemic recipients who were traced were examined by sequencing and cloning to determine the extent of virus diversity in hypervariable region 1. Serum-derived viral isolates were studied from the donor when his HCV infection was discovered in 1993, in his recipients that year (0.3-5 years post-transfusion) and 5 years later in the donor and six viraemic recipients who were still alive. Viral variants of broad diversity were readily demonstrated in the baseline samples of the donor (nucleotide p-distance 0.130), but significantly less (P<0.00003) diversity was observed in the recipients' first samples (p-distances within recipients 0.003-0.062). In the first blood samples of the recipients, many of the viral variants identified were closely related to a strain variant from the donor. In follow-up samples drawn 5 years later from the donor and six recipients, the p-distance among donor clones had increased (0.172, P<0.0005) compared with the recipients, who displayed significantly narrower quasispecies (0.011-0.086). A common finding was that recipients of blood components processed from the same donation differed substantially in persisting HCV infectious sequence. Markedly few changes leading to changes of amino acids had occurred during follow-up in four of six recipients. These results question the significance of the development of viral variants as a necessary phenomenon in the evolution of HCV and pathogenesis of the disease.

摘要

通过测序和克隆技术,对来自一名受感染献血者以及追踪到的13名病毒血症接受者的丙型肝炎病毒(HCV)变体进行了检测,以确定高变区1中病毒的多样性程度。研究了1993年发现该献血者感染HCV时其血清来源的病毒分离株,以及当年其接受者(输血后0.3 - 5年)的病毒分离株,5年后又研究了该献血者以及6名仍存活的病毒血症接受者的病毒分离株。在献血者的基线样本中很容易证明存在广泛多样的病毒变体(核苷酸p距离为0.130),但在接受者的首次样本中观察到的多样性显著较少(P<0.00003)(接受者内部的p距离为0.003 - 0.062)。在接受者的首次血液样本中,鉴定出的许多病毒变体与来自献血者的一个毒株变体密切相关。在5年后从献血者和6名接受者采集的后续样本中,与接受者相比,献血者克隆之间的p距离增加了(0.172,P<0.0005),接受者显示出明显更窄的准种(0.011 - 0.086)。一个常见的发现是,来自同一献血处理的血液成分的接受者在持续的HCV感染序列方面存在很大差异。在6名接受者中的4名接受者的随访期间,导致氨基酸变化的明显变化很少发生。这些结果质疑了病毒变体的发展作为HCV进化和疾病发病机制中必要现象的重要性。

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