Spike protein fusion peptide and feline coronavirus virulence.

Spike protein fusion peptide and feline coronavirus virulence.
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DOI:
10.3201/eid1807.120143
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发表时间:
2012-07
影响因子:
11.8
通讯作者:
Rottier PJ
Rottier PJ
中科院分区:
医学2区
文献类型:
--
作者:
Chang HW;Egberink HF;Halpin R;Spiro DJ;Rottier PJ

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突变可以不规律地发生,并伴随向性变化,导致不可预测的新疾病。众所周知,冠状病毒有可能改变宿主或组织嗜性,导致不可预测的新疾病和致病性变化;严重急性呼吸系统综合症和猫冠状病毒分别是最常见的例子。猫冠状病毒有两种致病类型:在肠上皮细胞中复制的非致病性猫肠冠状病毒(fecv)和在巨噬细胞中复制的致死性猫传染性腹膜炎病毒(fipv)。有证据表明FIPV起源于FECV突变,但尚未建立一致的区别差异。我们对每种致病型的11种病毒进行了全基因组测序,然后通过对该区域的数百种病毒进行额外测序,将重点放在最独特的单个位点上。结果,我们在刺突蛋白的推定融合肽中发现了2个氨基酸差异,这些差异共同将FIPV与FECV区分开来,在95%的病例中。通过这些或其他突变,病毒显然获得了巨噬细胞的亲和性并进行了全身传播。
Mutations can occur erratically and accompany tropism changes, resulting in unpredictable new diseases. Coronaviruses are well known for their potential to change their host or tissue tropism, resulting in unpredictable new diseases and changes in pathogenicity; severe acute respiratory syndrome and feline coronaviruses, respectively, are the most recognized examples. Feline coronaviruses occur as 2 pathotypes: nonvirulent feline enteric coronaviruses (FECVs), which replicate in intestinal epithelium cells, and lethal feline infectious peritonitis viruses (FIPVs), which replicate in macrophages. Evidence indicates that FIPV originates from FECV by mutation, but consistent distinguishing differences have not been established. We sequenced the full genome of 11 viruses of each pathotype and then focused on the single most distinctive site by additionally sequencing hundreds of viruses in that region. As a result, we identified 2 alternative amino acid differences in the putative fusion peptide of the spike protein that together distinguish FIPV from FECV in >95% of cases. By these and perhaps other mutations, the virus apparently acquires its macrophage tropism and spreads systemically.
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