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临床多瘤病毒 BK 变体与缺失的辅助基因是非功能性的,但可通过转互补作用恢复功能。

Clinical polyomavirus BK variants with agnogene deletion are non-functional but rescued by trans-complementation.

机构信息

Department of Microbiology and Virology, Institute of Medical Biology, University of Tromsø, Tromsø, Norway.

出版信息

Virology. 2010 Mar 1;398(1):12-20. doi: 10.1016/j.virol.2009.11.029. Epub 2009 Dec 14.

DOI:10.1016/j.virol.2009.11.029
PMID:20005552
Abstract

High-level replication of polyomavirus BK (BKV) in kidney transplant recipients is associated with the emergence of BKV variants with rearranged (rr) non-coding control region (NCCR) increasing viral early gene expression and cytopathology. Cloning and sequencing revealed the presence of a BKV quasispecies which included non-functional variants when assayed in a recombinant virus assay. Here we report that the rr-NCCR of BKV variants RH-3 and RH-12, both bearing a NCCR deletion including the 5' end of the agnoprotein coding sequence, mediated early and late viral reporter gene expression in kidney cells. However, in a recombinant virus they failed to produce infectious progeny despite large T-antigen and VP1 expression and the formation of nuclear virus-like particles. Infectious progeny was generated when the agnogene was reconstructed in cis or agnoprotein provided in trans from a co-existing BKV rr-NCCR variant. We conclude that complementation can rescue non-functional BKV variants in vitro and possibly in vivo.

摘要

高危型多瘤病毒 BK(BKV)在肾移植受者中的复制与出现具有重排(rr)非编码控制区(NCCR)的 BKV 变异体有关,这会增加病毒早期基因表达和细胞病变。克隆和测序显示,在重组病毒检测中,存在一种 BKV 准种,包括无功能的变异体。在这里,我们报告称,BKV 变异体 RH-3 和 RH-12 的 rr-NCCR 均携带包括 agnoprotein 编码序列 5'端在内的 NCCR 缺失,可在肾细胞中介导早期和晚期病毒报告基因的表达。然而,在重组病毒中,尽管存在大量的 T 抗原和 VP1 表达以及核病毒样颗粒的形成,它们仍未能产生感染性后代。当 agnogene 在顺式或由共存的 BKV rr-NCCR 变异体提供的转位中重建时,可产生感染性后代。我们得出结论,互补可以在体外和可能在体内拯救无功能的 BKV 变异体。

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