GENOME SEQUENCES OF A MOUSE-AVIRULENT AND A MOUSE-VIRULENT STRAIN OF ROSS RIVER VIRUS
GENOME SEQUENCES OF A MOUSE-AVIRULENT AND A MOUSE-VIRULENT STRAIN OF ROSS RIVER VIRUS
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DOI：
10.1016/0042-6822(88)90292-9
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发表时间：
1988-04-01
期刊：
影响因子：
3.7
通讯作者：
DALGARNO, L
中科院分区：
文献类型：
--
作者：
FARAGHER, SG;MEEK, ADJ;DALGARNO, L
罗斯河病毒的小鼠无毒毒株RRV NB5092（分离于1969年）的基因组RNA的核苷酸序列已经确定，而原型小鼠毒性毒株RRV T48（分离于1959年）的相应序列已经完成。RRV NB5092基因组的长度约为11,674个核苷酸，而RRV T48基因组的长度为11,853个核苷酸。RRV NB5092和RRV T48具有相同的基因组组织。对于这两种病毒，基因组5'端都有一个80个核苷酸的未翻译区，随后是一个7440个核苷酸的开放阅读框，在5586个核苷酸后被一个蛋白石终止密码子打断。通过与其他甲型病毒的同源性，5586个核苷酸的开放阅读框编码非结构蛋白nsP1、nsP2和nsP3；第四种非结构蛋白nsP4是通过解读蛋白石密码子产生的。RRV非结构蛋白在大小、净电荷和亲水特性方面与Sindbis病毒和Semliki森林病毒的相应蛋白具有很强的同源性。然而，蛋白质之间或蛋白质内部的同源性并不均匀；nsP1、nsP2和nsP4的扩展结构域在甲病毒之间具有高度保守性，而nsP3的c端区域在甲病毒之间的序列和长度上几乎没有保守性。一个由44个核苷酸（RRV NB5092）或47个核苷酸（RRV T48）组成的未翻译“连接”区将非结构蛋白编码区和结构蛋白编码区分开。结构蛋白（衣壳- e3 - e2 - 6k - e1）从一个包含3762个核苷酸的开放阅读框中翻译出来，随后是一个包含大约348个核苷酸（RRV NB5092）或524个核苷酸（RRV T48）的3‘’未翻译区。排除缺失和插入，RRV NB5092和RRV T48的基因组差异为284个核苷酸，序列差异为2.38%。与RRV T48相比，RRV NB5092仅在非编码区发现序列缺失或插入，包括在3''-非翻译区缺失173个核苷酸。在编码区，大部分核苷酸差异是沉默的；在非结构蛋白中有36个氨基酸差异，在结构蛋白中有12个氨基酸差异。两种RRV毒株之间氨基酸差异的分布与α病毒之间序列保守性较差的结构域的位置有关。讨论了包膜糖蛋白E1和E2的氨基酸差异在RRV NB5092和RRV T48不同抗原性和生物学特性中的可能作用。
The nucleotide sequence of the genomic RNA of a mouse-avirulent strain of Ross River virus, RRV NB5092 (isolated in 1969), has been determined and the corresponding sequence for the prototype mouse-virulent strain, RRV T48 (isolated in 1959), has been completed. The RRV NB5092 genome is approximately 11,674 nucleotides in length, compared with 11,853 nucleotides for RRV T48. RRV NB5092 and RRV T48 have the same genome organization. For both viruses an untranslated region of 80 nucleotides at the 5'' end of the genome is followed by a 7440-nucleotide open reading frame which is interrupted after 5586 nucleotides by a single opal termination codon. By homology with other alphaviruses, the 5586-nucleotide open reading frame encodes the nonstructural proteins nsP1, nsP2, and nsP3; a fourth nonstructural protein, nsP4, is produced by read-through of the opal codon. The RRV nonstructural proteins show strong homology with the corresponding proteins of Sindbis virus and Semliki Forest virus in terms of size, net charge, and hydropathy characteristics. However, homology is not uniform between or within the proteins; nsP1, nsP2, and nsP4 contain extended domains which are highly conserved between alphaviruses, while the C-terminal region of nsP3 shows little conservation in sequence or length between alphaviruses. An untranslated "junction" region of 44 nucleotides (for RRV NB5092) or 47 nucleotides (for RRV T48) separates the nonstructural and structural protein coding regions. The structural proteins (capsid-E3-E2-6K-E1) are translated from an open reading frame of 3762 nucleotides which is followed by a 3''-untranslated region of approximately 348 nucleotides (for RRV NB5092) or 524 nucleotides (for RRV T48). Excluding deletions and insertions, the genomes of RRV NB5092 and RRV T48 differ at 284 nucleotides, representing a sequence divergence of 2.38%. Sequence deletions or insertions were found only in the noncoding regions and include a 173-nucleotide deletion in the 3''-untranslated region of RRV NB5092, compared with RRV T48. In the coding regions, most of the nucleotide differences are silent; there are 36 amino acid differences in the nonstructural proteins and 12 in the structural proteins. The distribution of amino acid differences between the two RRV strains correlates with the location of domains which are poorly conserved in sequence between alphaviruses. The possible role of amino acid differences in envelope glycoproteins E1 and E2 in determining the different antigenic and biological properties of RRV NB5092 and RRV T48 is discussed.