Oberste M S, Parker M D, Smith J F
Virology Division, U.S. Army Medical Research Institute of Infectious Diseases, Ft. Detrick, Frederick, Maryland 21702-5011, USA.
Virology. 1996 May 1;219(1):314-20. doi: 10.1006/viro.1996.0254.
The complete nuleotide and predicted amino acid sequences of Venezuelan equine encephalitis (VEE) virus subtype IE (isolate 68U201) were determined and compared to those of other antigenic variants within the VEE complex, strains IAB-TrD, IC-P676, ID-3880, IE-Menall, and II-Fe3-7c. The 68U201 structural proteins were most closely related to their Menall counterparts (97--100% identity) and more distantly related to VEE strains of other antigenic varieties (83--93% identity). With the exception of nsP3, the 68U201 nonstructural proteins were 94--95% identical to those of TrD, P676, and 3880 (nonstructural gene sequences are not available for Menall and Fe3-7c). The amino-terminal region of nsP3 (aa 1--329), which is highly conserved among all alphaviruses, was 93--94% identical for all VEE strains. The nsP3 carboxyl region is highly divergent among alphaviruses in general, but well conserved among previously sequenced VEE strains (>90% identity). Surprisingly, the carboxyl region of 68U201 nsP3 (aa 330--563) was only 59--61% identical to that of subtype IAB, IC, and ID viruses, with large insertions and deletions in addition to numerous substitutions. The differences between the 68U201 and other VEE nsP3 carboxyl regions were not randomly distributed, as there were four domains of high similarity within the nonconserved region. To examine this divergence more closely, we sequenced a portion of the Menall ns3 gene. The 68U201 and Menall nsP3 nonconserved regions were 85.3% identical and had the same basic domain structure, which was distinct from the IAB, IC, and ID nsP3 proteins, suggesting that the domain structure of nsP3 may be subtype/variety-specific. VEE nsP3 sequence diversity may reflect ecological differences such as adaptation to different mosquito vectors or vertebrate hosts.
测定了委内瑞拉马脑炎（VEE）病毒IE亚型（毒株68U201）的完整核苷酸序列和预测的氨基酸序列，并与VEE病毒复合群内的其他抗原变异株（IAB-TrD、IC-P676、ID-3880、IE-Menall和II-Fe3-7c毒株）的序列进行了比较。68U201的结构蛋白与其Menall对应蛋白最为相似（同一性为97%-100%），与其他抗原变种的VEE毒株的亲缘关系较远（同一性为83%-93%）。除nsP3外，68U201的非结构蛋白与TrD、P676和3880的非结构蛋白同一性为94%-95%（Menall和Fe3-7c没有非结构基因序列）。nsP3的氨基末端区域（氨基酸1-329）在所有甲病毒中高度保守，所有VEE毒株的该区域同一性为93%-94%。一般来说，nsP3的羧基区域在甲病毒中高度分化，但在先前测序的VEE毒株中保守性良好（同一性>90%）。令人惊讶的是，68U201 nsP3的羧基区域（氨基酸330-563）与IAB、IC和ID亚型病毒的该区域同一性仅为59%-61%，除了大量替换外，还有大的插入和缺失。68U201与其他VEE nsP3羧基区域之间的差异并非随机分布，因为在非保守区域内有四个高度相似的结构域。为了更仔细地研究这种差异，我们对Menall ns3基因的一部分进行了测序。68U201和Menall nsP3的非保守区域同一性为85.3%，并且具有相同的基本结构域结构，这与IAB、IC和ID nsP3蛋白不同，表明nsP3的结构域结构可能是亚型/变种特异性的。VEE nsP3序列多样性可能反映了生态差异，如对不同蚊媒或脊椎动物宿主的适应性。
