Altered pathogenicity, immunogenicity, tissue tropism and 3'-7kb region sequence of an avian infectious bronchitis coronavirus strain after serial passage in embryos.

Altered pathogenicity, immunogenicity, tissue tropism and 3'-7kb region sequence of an avian infectious bronchitis coronavirus strain after serial passage in embryos.
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DOI:
10.1016/j.vaccine.2009.05.072
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发表时间:
2009-07-23
期刊:
影响因子:
5.5
通讯作者:
Kong X
Kong X
中科院分区:
医学3区
文献类型:
--
作者:
Liu S;Zhang X;Gong L;Yan B;Li C;Han Z;Shao Y;Li H;Kong X

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本研究采用鸡胚连续传代的方法,对我国LX 4型肾型传染性支气管炎病毒(IBV)CK/CH/LHLJ/04 V株进行了致弱研究。CK/CH/LHLJ/04 V株系3′ ~ 7 kb区序列分析表明,该株系中含有多个变异株。在连续传代过程中,病毒滴度逐渐升高,但在鸡体内的复制能力下降。病毒在第40代(P40)和P70时部分减毒,在P110时完全减毒。在P110和P70时分别失去免疫原性和肾嗜性。在3′-7kb区域发现了氨基酸替换,主要是在刺突蛋白(S)中。S1亚基的置换发生在P3和P40之间,并且病毒传代中的所有亚群显示出相同的置换。然而,发生在P70和P110之间的其他替换仅在病毒传代的某些亚群中发现。在P70和P110的大多数亚群中均发现3′-UTR有109 bp的缺失,这可能与病毒的复制、转录和致病性有关。病毒3′ ~ 7 kb区域的变化可能是导致病毒减毒、免疫原性降低和组织嗜性改变的原因,但我们不能排除基因组其他部分也可能参与这些变化。
In this study, we attenuated a Chinese LX4-type nephropathogenic infectious bronchitis virus (IBV) strain, CK/CH/LHLJ/04V, by serial passage in embryonated chicken eggs. Based on sequence analysis of the 3′-7 kb region, the CK/CH/LHLJ/04V virus population contained subpopulations with a mixture of genetic mutants. The titers of the virus increased gradually during serial passage, but the replication capacity decreased in chickens. The virus was partially attenuated at passage 40 (P40) and P70, and was fully attenuated at P110. It lost immunogenicity and kidney tropism at P110 and P70, respectively. Amino acid substitutions were found in the 3′-7 kb region, primarily in the spike (S) protein. Substitutions in the S1 subunit occurred between P3 and P40 and all subpopulations in a virus passage showed the same substitutions. Other substitutions that occurred between P70 and P110, however, were found only in some subpopulations of the virus passages. A 109-bp deletion in the 3′-UTR was observed in most subpopulations of P70 and P110, and might be related to virus replication, transcription and pathogenicity. The changes described in the 3′-7 kb region of the virus are possibly responsible for virus attenuation, immunogenicity decrease and tissue tropism changes; however, we cannot exclude the possibility that other parts of the genome may also be involved in those changes.
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