Inverso J A, De Gee A L, Mansfield J M
Department of Veterinary Science, University of Wisconsin, Madison 53706.
J Immunol. 1988 Jan 1;140(1):289-93.
The question of linkage of virulence traits to variable surface glycoprotein (VSG) expression in African trypanosomiasis was addressed. Previously we demonstrated that daughter cells arising in mice infected with a genetically homogeneous trypanosome population of Trypanosoma brucei rhodesiense were more virulent than the infecting population (J. A. Inverso and J. M. Mansfield, J. Immunol. 130:412, 1983). These virulent trypanosomes expressed differences in surface phenotype compared with the infecting variant types, and we proposed that virulence may be "linked" to VSG expression. In the present study, however, we have shown that expression of virulence is independent of the VSG phenotype displayed by trypanosome populations. A VSG-identical but highly virulent subpopulation of T. b. rhodesiense LouTat 1 was derived by rapid subpassage and subcloning in immunosuppressed mice. The virulent LouTat 1A subclone derived in this manner killed B10.BR/SgSnJ mice in 3 to 4 days postinfection compared with approximately 60 days for the parent clone, LouTat 1. The virulent subclone LouTat 1A appears to express the same VSG as the less virulent LouTat 1 population, as determined by polyspecific and monoclonal antibody-binding assays, cross-protection tests, and amino acid sequence analyses of the N-terminal portion of the VSG molecules. When LouTat 1 and subclone LouTat 1A were injected into a heterologous host species, multiple variant antigenic types (VATs) arising from each inoculum were isolated and characterized. VATs derived from the virulent subclone were as uniformly virulent for B10.BR mice as LouTat 1A. In summary, these results demonstrate that trypanosome virulence, once expressed, is a stable phenotype that does not seem to be associated with a particular VSG phenotype, nor does virulence change with the expression of different VSG genes.
我们研究了非洲锥虫病中毒力特征与可变表面糖蛋白（VSG）表达之间的联系问题。此前我们证明，感染了遗传同质的布氏罗得西亚锥虫群体的小鼠体内产生的子代细胞比感染群体更具毒力（J. A. Inverso和J. M. Mansfield，《免疫学杂志》130:412，1983）。与感染的变异类型相比，这些有毒力的锥虫在表面表型上存在差异，我们推测毒力可能与VSG表达“相关”。然而，在本研究中，我们表明毒力的表达与锥虫群体所展示的VSG表型无关。通过在免疫抑制小鼠中快速传代和亚克隆，获得了布氏罗得西亚锥虫LouTat 1的一个VSG相同但毒力很强的亚群体。以这种方式获得的有毒力的LouTat 1A亚克隆在感染后3至4天就可杀死B10.BR/SgSnJ小鼠，而亲本克隆LouTat 1则需要大约60天。通过多特异性和单克隆抗体结合试验、交叉保护试验以及VSG分子N端部分的氨基酸序列分析确定，有毒力的亚克隆LouTat 1A似乎与毒力较弱的LouTat 1群体表达相同的VSG。当将LouTat 1和亚克隆LouTat 1A注射到异源宿主物种中时，从每个接种物中分离并鉴定出了多种变异抗原类型（VAT）。来自有毒力亚克隆的VAT对B10.BR小鼠的毒力与LouTat 1A一样均一。总之，这些结果表明，锥虫毒力一旦表达就是一种稳定的表型，似乎与特定的VSG表型无关，毒力也不会随不同VSG基因的表达而改变。
