S1 Subunit of Spike Protein from a Current Highly Virulent Porcine Epidemic Diarrhea Virus Is an Important Determinant of Virulence in Piglets.

S1 Subunit of Spike Protein from a Current Highly Virulent Porcine Epidemic Diarrhea Virus Is an Important Determinant of Virulence in Piglets.
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DOI:
10.3390/v10090467
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发表时间:
2018-08-30
期刊:
Viruses
影响因子:
--
通讯作者:
Kamitani W
Kamitani W
中科院分区:
其他
文献类型:
--
作者:
Suzuki T;Terada Y;Enjuanes L;Ohashi S;Kamitani W

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根据编码S蛋白的S基因序列,我们此前鉴定了自2013年以来在日本重新出现的三种不同类型的猪流行性腹泻病毒(猪流行性腹泻病毒),即北美型、S Indel型和S大DEL型。基于对北美和S大毒株的实验感染,我们还假设PEDV的毒力可能与S蛋白的S1亚基有关。为了验证这一假设,我们现在已经在诺生仔猪身上测试了由反向遗传学产生的各种重组PEDV。在国家动物卫生研究所饲养的接种了CV777的仔猪,以及感染了相同病毒的重组形式的仔猪,出现了亚临床到轻度腹泻。相比之下,接种S基因部分或全部替换为日本PEDV强毒株OKN-1/JPN/2013的相应序列的重组毒株接种仔猪后,出现严重的水样腹泻、脱水、体重减轻、生长迟缓和高死亡率。事实上,症状与接种OKN-1/JPN/2013的仔猪相似,在较小的仔猪中尤为明显。综上所述,这些数据表明,S蛋白的S1亚基是决定PEDV毒力的重要因素,并推动了新疫苗候选的开发。
Base on the sequence of S genes, which encode spike proteins, we previously identified three different types (North American, S INDEL, and S large-DEL types) of porcine epidemic diarrhea virus (PEDV) that have re-emerged in Japan since 2013. Based on experimental infections with the North American and S large-DEL types, we also hypothesized that PEDV virulence may be linked to the S1 subunit of the S protein. To test this hypothesis, we have now assayed in gnotobiotic piglets various recombinant PEDVs generated by reverse genetics. Piglets inoculated with CV777 maintained in National Institute of Animal Health, along with piglets infected with a recombinant form of the same virus, developed subclinical to mild diarrhea. In contrast, severe watery diarrhea, dehydration, weight loss, astasia, and high mortality were observed in piglets inoculated with recombinant strains in which the S gene was partially or fully replaced with corresponding sequences from the highly virulent Japanese PEDV isolate OKN-1/JPN/2013. Indeed, symptoms resembled those in piglets inoculated with the OKN-1/JPN/2013, and were especially pronounced in younger piglets. Collectively, the data demonstrate that the S1 subunit of the S protein is an important determinant of PEDV virulence, and advance development of new vaccine candidate.
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