Faragher S G, Meek A D, Rice C M, Dalgarno L
Biochemistry Department, Faculty of Science, Australian National University, Canberra.
Virology. 1988 Apr;163(2):509-26. doi: 10.1016/0042-6822(88)90292-9.
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.
已确定一株对小鼠无毒力的罗斯河病毒（RRV NB5092，1969年分离）基因组RNA的核苷酸序列，并完成了原型小鼠毒力株RRV T48（1959年分离）的相应序列测定。RRV NB5092基因组长度约为11,674个核苷酸，而RRV T48为11,853个核苷酸。RRV NB5092和RRV T48具有相同的基因组结构。对于这两种病毒，基因组5'端有一个80个核苷酸的非翻译区，其后是一个7440个核苷酸的开放阅读框，该阅读框在5586个核苷酸后被一个单一的乳白终止密码子中断。通过与其他甲病毒的同源性分析，5586个核苷酸的开放阅读框编码非结构蛋白nsP1、nsP2和nsP3；第四个非结构蛋白nsP4是通过乳白密码子的通读产生的。RRV的非结构蛋白在大小、净电荷和疏水性特征方面与辛德毕斯病毒和Semliki森林病毒的相应蛋白具有很强的同源性。然而，这些蛋白之间或内部的同源性并不一致；nsP1、nsP2和nsP4包含在甲病毒之间高度保守的延伸结构域，而nsP3的C末端区域在甲病毒之间的序列或长度上几乎没有保守性。一个44个核苷酸（对于RRV NB5092）或47个核苷酸（对于RRV T48）的非翻译“连接”区域将非结构蛋白和结构蛋白编码区域分开。结构蛋白（衣壳-E3-E2-6K-E1）由一个3762个核苷酸的开放阅读框翻译而来，其后是一个约348个核苷酸（对于RRV NB5092）或524个核苷酸（对于RRV T48）的3'非翻译区。排除缺失和插入，RRV NB5092和RRV T48的基因组在284个核苷酸处存在差异，代表序列差异为2.38%。序列缺失或插入仅在非编码区发现，包括与RRV T48相比，RRV NB5092的3'非翻译区有一个173个核苷酸的缺失。在编码区，大多数核苷酸差异是沉默的；非结构蛋白中有36个氨基酸差异，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甲病毒之间序列保守性较差的结构域位置相关。讨论了包膜糖蛋白E1和E2中的氨基酸差异在决定RRV NB5092和RRV T48不同抗原性和生物学特性方面的可能作用。
