Fultz P N
Department of Microbiology, University of Alabama, Birmingham 35294.
J Virol. 1991 Sep;65(9):4902-9. doi: 10.1128/JVI.65.9.4902-4909.1991.
A variant of simian immunodeficiency virus from sooty mangabey monkeys (SIVsmm), termed SIVsmmPBj14, was previously identified and shown to induce acute disease and death within 1 to 2 weeks of inoculation of pig-tailed macaques and mangabey monkeys (P. N. Fultz, H. M. McClure, D. C. Anderson, and W. M. Switzer, AIDS Res. Hum. Retroviruses 5:397-409, 1989). SIVsmmPBj14 differed from its parent virus, SIVsmm9, not only in pathogenicity but also in multiple in vitro properties. As a first approach to understanding the biological and molecular mechanisms responsible for the acute disease and death induced by this variant, virus-host cell interactions of SIVsmmPBj14 and SIVsmm9 were studied. Initial rates of replication of the two viruses were identical in primary peripheral blood mononuclear cells (PBMC) from normal pig-tailed macaques and mangabey monkeys, but SIVsmmPBj14 infection always resulted in higher yields of virus than did SIVsmm9 infection, as assessed by levels of reverse transcriptase activity in culture supernatants. Surprisingly, despite its cytopathicity for macaque and mangabey CD4+ cells, replication of SIVsmmPBj14 was accompanied by up to 10-fold increases in number of viable cells compared with cell numbers in uninfected or SIVsmm9-infected cultures. Furthermore, SIVsmmPBj14 was shown to infect and replicate in resting PBMC just as efficiently as in mitogen-stimulated PBMC, irrespective of whether exogenous interleukin-2 (IL-2) or antibodies that neutralized IL-2 were added to culture media. Accumulation of virus in culture supernatants of resting PBMC preceded by several days the appearance of activated cells which expressed the IL-2 receptor alpha subunit (CD25), suggesting that activation of cells was not essential for replication. The ability to activate and to induce simian PBMC to proliferate appeared specific for the acutely lethal variant because incorporation of [3H]thymidine by PBMC from naive animals was observed only upon incubation with concentrated, heat-inactivated SIVsmmPBj14 and not with other viruses. Both CD4(+)- and CD8(+)-enriched cell populations proliferated in response to SIVsmmPBj14. These results are consistent with in vivo observations and suggest that the abilities both to replicate in resting cells and to induce lymphocytes to proliferate may contribute to the extreme virulence of SIVsmmPBj14.
一种来自乌黑白眉猴的猿猴免疫缺陷病毒变体（SIVsmm），称为SIVsmmPBj14，此前已被鉴定出来，并显示在接种猪尾猕猴和白眉猴后的1至2周内可引发急性疾病并导致死亡（P.N.富尔茨、H.M.麦克卢尔、D.C.安德森和W.M.斯威策，《艾滋病研究与人类逆转录病毒》5:397 - 409，1989年）。SIVsmmPBj14与其亲本病毒SIVsmm9不仅在致病性上不同，而且在多种体外特性上也不同。作为理解该变体引发急性疾病和死亡的生物学及分子机制的第一步，对SIVsmmPBj14和SIVsmm9的病毒 - 宿主细胞相互作用进行了研究。两种病毒在来自正常猪尾猕猴和白眉猴的原代外周血单核细胞（PBMC）中的初始复制速率相同，但通过培养上清液中逆转录酶活性水平评估，SIVsmmPBj14感染产生的病毒产量总是高于SIVsmm9感染。令人惊讶的是，尽管SIVsmmPBj14对猕猴和白眉猴的CD4 + 细胞具有细胞病变效应，但其复制伴随着活细胞数量比未感染或SIVsmm9感染的培养物中的细胞数量增加多达10倍。此外，无论是否向培养基中添加外源性白细胞介素 - 2（IL - 2）或中和IL - 2的抗体，SIVsmmPBj14在静息PBMC中的感染和复制效率都与在有丝分裂原刺激的PBMC中一样高。静息PBMC培养上清液中病毒的积累比表达IL - 2受体α亚基（CD25）的活化细胞的出现提前几天，这表明细胞活化对于复制并非必需。激活并诱导猿猴PBMC增殖的能力似乎是这种急性致死变体所特有的，因为仅在与浓缩的、热灭活的SIVsmmPBj14孵育时才观察到来自未接触过该病毒动物的PBMC掺入[3H]胸腺嘧啶，而与其他病毒孵育时未观察到这种现象。富含CD4(+)和CD8(+)的细胞群体都对SIVsmmPBj14产生增殖反应。这些结果与体内观察结果一致，并表明在静息细胞中复制以及诱导淋巴细胞增殖的能力可能有助于SIVsmmPBj14的极端毒力。
