Courgnaud V, Lauré F, Fultz P N, Montagnier L, Bréchot C, Sonigo P
Institut National de la Santé et de la Recherche Médicale U75 CHU Necker, Paris, France.
J Virol. 1992 Jan;66(1):414-9. doi: 10.1128/JVI.66.1.414-419.1992.
We determined the nucleotide sequences of two related isolates of simian immunodeficiency virus from the sooty mangabey monkey (SIVsmm) that exhibit dramatic differences in virulence. These isolates are separated by one experimental cross-species transmission, from sooty mangabey to pig-tailed macaque. The parental virus (SIVsmm9), nonpathogenic in the original host (sooty mangabeys), causes a chronic AIDS-like disease in macaques. In contrast, the variant virus (SIVsmmPBj14) induces an acute lethal disease in various macaque species and is also pathogenic for sooty mangabeys. The combination of necessary and sufficient mutations that determined the acutely lethal phenotype on the SIVsmm9 genetic background is included within a maximal set of 57 point mutations, plus two insertions located in the long terminal repeat (22 bp spanning an NF-kappa B-like enhancer element) and in the surface envelope glycoprotein (5 amino acids). Comparisons of synonymous and nonsynonymous nucleotide substitutions in the genome of SIVsmm indicated that selective pressures, probably due to the host immune response, favored amino acid changes in the envelope. This immunoevolutionary mechanism could explain the increase in diversity and the apparition of new virulent phenotypes after cross-species transmission.
我们测定了来自乌黑白眉猴的两种相关猿猴免疫缺陷病毒（SIVsmm）分离株的核苷酸序列，这两种分离株在毒力上表现出显著差异。这两种分离株通过一次从乌黑白眉猴到豚尾猕猴的实验性跨物种传播而分开。亲本病毒（SIVsmm9）在原始宿主（乌黑白眉猴）中无致病性，但在猕猴中会引发慢性艾滋病样疾病。相比之下，变异病毒（SIVsmmPBj14）在各种猕猴物种中诱发急性致死性疾病，并且对乌黑白眉猴也具有致病性。在SIVsmm9遗传背景上决定急性致死表型的必要和充分突变组合包含在最多57个点突变的集合中，另外还有两个插入突变，一个位于长末端重复序列（跨越一个NF-κB样增强子元件的22 bp），另一个位于表面包膜糖蛋白（5个氨基酸）中。对SIVsmm基因组中同义核苷酸替换和非同义核苷酸替换的比较表明，可能由于宿主免疫反应导致的选择压力有利于包膜中的氨基酸变化。这种免疫进化机制可以解释跨物种传播后多样性的增加和新的毒力表型的出现。
