Hutchinson O Clyde, Picozzi Kim, Jones Nicola G, Mott Helen, Sharma Reuben, Welburn Susan C, Carrington Mark
Department of Biochemistry, 80 Tennis Court Road, Cambridge, CB2 1GA, UK.
BMC Genomics. 2007 Jul 13;8:234. doi: 10.1186/1471-2164-8-234.
In a mammalian host, the cell surface of African trypanosomes is protected by a monolayer of a single variant surface glycoprotein (VSG). The VSG is central to antigenic variation; one VSG gene is expressed at any one time and there is a low frequency stochastic switch to expression of a different VSG gene. The genome of Trypanosoma brucei contains a repertoire of > 1000 VSG sequences. The degree of conservation of the genomic VSG repertoire in different strains has not been investigated in detail.
Eighteen expressed VSGs from Ugandan isolates were compared with homologues (> 40 % sequence identity) in the two available T. brucei genome sequences. Fourteen homologues were present in the genome of Trypanosoma brucei brucei TREU927 from Kenya and fourteen in the genome of T. b. gambiense Dal972 from Cote d'Ivoire. The Ugandan VSGs averaged 71% and 73 % identity to homologues in T. b. brucei and T. b. gambiense respectively. The sequence divergence between homologous VSGs from the three different strains was not random but was more prevalent in the parts of the VSG believed to interact with the host immune system on the living trypanosome.
It is probable that the VSG repertoires in the different isolates contain many common VSG genes. The location of divergence between VSGs is consistent with selection for strain-specific VSG repertoires, possibly to allow superinfection of an animal by a second strain. A consequence of strain-specific VSG repertoires is that any vaccine based on large numbers of VSGs from a single strain will only provide partial protection against other strains.
在哺乳动物宿主体内，非洲锥虫的细胞表面由单层单一可变表面糖蛋白（VSG）保护。VSG是抗原变异的核心；在任何时刻只有一个VSG基因表达，并且会以低频率随机切换到另一个VSG基因的表达。布氏锥虫的基因组包含超过1000个VSG序列。尚未详细研究不同菌株中基因组VSG库的保守程度。
将来自乌干达分离株的18个表达的VSG与两个可用的布氏锥虫基因组序列中的同源物（序列同一性>40%）进行比较。在来自肯尼亚的布氏布氏锥虫TREU927基因组中有14个同源物，在来自科特迪瓦的布氏冈比亚锥虫Dal972基因组中有14个同源物。乌干达的VSG与布氏布氏锥虫和布氏冈比亚锥虫中的同源物平均序列同一性分别为71%和73%。来自三种不同菌株的同源VSG之间的序列差异并非随机分布，而是在VSG中被认为与活锥虫的宿主免疫系统相互作用的部分更为普遍。
不同分离株中的VSG库可能包含许多共同的VSG基因。VSG之间差异的位置与菌株特异性VSG库的选择一致，可能是为了允许动物被第二种菌株再次感染。菌株特异性VSG库的一个后果是，任何基于来自单一菌株的大量VSG的疫苗只能提供针对其他菌株的部分保护。
