Aguado B, Selmes I P, Smith G L
Sir William Dunn School of Pathology, University of Oxford, U.K.
J Gen Virol. 1992 Nov;73 ( Pt 11):2887-902. doi: 10.1099/0022-1317-73-11-2887.
A 21.8 kbp region of the genome of variola major virus (strain Harvey), a virus that caused haemorrhagic-type smallpox, has been sequenced and shown to possess 96% nucleotide identity to the corresponding region of vaccinia virus, the smallpox vaccine. Overall the gene arrangement in the two viruses is highly similar and individual open reading frames (ORFs) display a high degree of amino acid identity, for instance 26 of the 32 variola virus ORFs have > or = 90% identity with their vaccinia virus counterparts. A remarkable difference is the disruption of seven vaccinia virus ORFs into small fragments in variola virus. These include the variola virus homologue of vaccinia virus SalF2R, which encodes a protein related to C-type animal lectins, and SalF7L, which encodes an active 3 beta-hydroxysteroid dehydrogenase enzyme that contributes to vaccinia virus virulence. Upstream of the variola virus haemagglutinin gene there is a deletion of 1910 bp so that the equivalent of vaccinia virus gene SalF17R is truncated, and SalF16R, which shows amino acid similarity to the tumour necrosis factor receptor, is absent. The region sequenced includes the genes for thymidylate kinase and DNA ligase both of which are active in vaccinia virus and are highly conserved in variola virus. Other conserved ORFs with interesting homologies are those encoding profilin, superoxide dismutase and part of guanylate kinase. Two vaccinia virus genes encoding glycoproteins of the outer envelope of extracellular enveloped virus are also conserved in variola virus and this homology is likely to have contributed to the immunological protection which vaccinia virus evoked against smallpox. Lastly, there are multiple instances in which short oligonucleotide direct repeats flank a region absent from either variola or vaccinia virus.
导致出血型天花的天花病毒（哈维毒株）基因组中的一段21.8千碱基对区域已被测序，结果显示它与天花疫苗牛痘病毒的相应区域具有96%的核苷酸同一性。总体而言，这两种病毒的基因排列高度相似，各个开放阅读框（ORF）显示出高度的氨基酸同一性，例如，天花病毒的32个ORF中有26个与其牛痘病毒对应物的同一性≥90%。一个显著的差异是，牛痘病毒的7个ORF在天花病毒中被打断成小片段。其中包括牛痘病毒SalF2R的天花病毒同源物，它编码一种与C型动物凝集素相关的蛋白质，以及SalF7L，它编码一种活性3β-羟基类固醇脱氢酶，该酶对牛痘病毒的毒力有贡献。在天花病毒血凝素基因的上游有一个1910碱基对的缺失，使得相当于牛痘病毒基因SalF17R的部分被截断，并且与肿瘤坏死因子受体具有氨基酸相似性的SalF16R不存在。测序区域包括胸苷酸激酶和DNA连接酶的基因，这两个基因在牛痘病毒中都有活性，并且在天花病毒中高度保守。其他具有有趣同源性的保守ORF是那些编码肌动蛋白结合蛋白、超氧化物歧化酶和部分鸟苷酸激酶的基因。牛痘病毒中编码细胞外被膜病毒外膜糖蛋白的两个基因在天花病毒中也保守，这种同源性可能有助于牛痘病毒对天花产生的免疫保护作用。最后，有多个实例表明，短寡核苷酸直接重复序列位于天花病毒或牛痘病毒所没有的区域两侧。
