Human coronavirus 229E encodes a single ORF4 protein between the spike and the envelope genes.
Human coronavirus 229E encodes a single ORF4 protein between the spike and the envelope genes.
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DOI：
10.1186/1743-422x-3-106
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发表时间：
2006-12-28
期刊：
影响因子：
4.8
通讯作者：
van der Hoek, Lia
中科院分区：
文献类型：
--
作者：
Dijkman, Ronald;Jebbink, Maarten F;Wilbrink, Berry;Pyrc, Krzysztof;Zaaijer, Hans L;Minor, Philip D;Franklin, Sally;Berkhout, Ben;Thiel, Volker;van der Hoek, Lia
冠状病毒的基因组包含结构和非结构基因，包括几个所谓的辅助基因。除了人类冠状病毒（HCoV）229 E外，所有1b组冠状病毒都编码刺突和包膜基因之间的单一辅助蛋白。原型病毒有一个分裂基因，编码推定的ORF 4a和ORF 4 b蛋白。为了确定是否主要HCoV-229 E分离株表现出这种不寻常的基因组组织，我们分析了ORF 4a/B区域的5个目前的临床分离株从荷兰和3个早期分离株收集在普通感冒单位（CCU）在索尔兹伯里，英国。所有荷兰分离株的ORF 4a/B区在氨基酸水平上是相同的。所有CCU分离株在核苷酸水平上与荷兰分离株仅98%相同，但与原型HCoV-229 E更密切相关（>98%）。值得注意的是，我们的分析显示，实验室适应的原型HCoV-229 E在ORF 4 a/B区域中具有2个核苷酸的缺失，而所有临床分离株携带单个ORF，大小为660 nt，编码219个氨基酸的单个蛋白，其是由HCoV-NL 63和PEDV编码的ORF 3蛋白的同源物。因此，1b组冠状病毒HCoV-NL 63、PEDV和HCoV-229 E的基因组结构是相同的。HCoV-229 E实验室菌株的广泛培养可能导致ORF 4的截短。这可能表明该蛋白在细胞培养中不是必需的，但临床分离株中ORF 4蛋白的高度保守氨基酸序列表明该蛋白在体内起重要作用。
The genome of coronaviruses contains structural and non-structural genes, including several so-called accessory genes. All group 1b coronaviruses encode a single accessory protein between the spike and envelope genes, except for human coronavirus (HCoV) 229E. The prototype virus has a split gene, encoding the putative ORF4a and ORF4b proteins. To determine whether primary HCoV-229E isolates exhibit this unusual genome organization, we analyzed the ORF4a/b region of five current clinical isolates from The Netherlands and three early isolates collected at the Common Cold Unit (CCU) in Salisbury, UK. All Dutch isolates were identical in the ORF4a/b region at amino acid level. All CCU isolates are only 98% identical to the Dutch isolates at the nucleotide level, but more closely related to the prototype HCoV-229E (>98%). Remarkably, our analyses revealed that the laboratory adapted, prototype HCoV-229E has a 2-nucleotide deletion in the ORF4a/b region, whereas all clinical isolates carry a single ORF, 660 nt in size, encoding a single protein of 219 amino acids, which is a homologue of the ORF3 proteins encoded by HCoV-NL63 and PEDV. Thus, the genome organization of the group 1b coronaviruses HCoV-NL63, PEDV and HCoV-229E is identical. It is possible that extensive culturing of the HCoV-229E laboratory strain resulted in truncation of ORF4. This may indicate that the protein is not essential in cell culture, but the highly conserved amino acid sequence of the ORF4 protein among clinical isolates suggests that the protein plays an important role in vivo.