Pion M, Liska V, Chenine A L, Hofmann-Lehmann R, Vlasak J, Gondois-Rey F, Ruprecht R M, Hirsch I
Unité de Pathogénie des Infections à Lentivirus, INSERM U372, Parc Scientifique et Technologique de Luminy, 13273 Marseille, France.
Virology. 2001 Oct 10;289(1):103-13. doi: 10.1006/viro.2001.1079.
Using long-distance DNA PCR, we prospectively followed rhesus monkeys that had been inoculated intramuscularly with supercoiled plasmid DNA encoding intact simian immunodeficiency virus (SIV). From 4 to 10 weeks postinoculation onward, we detected extensively deleted proviral genomes along with full-length viral genomes in peripheral blood mononuclear cells (PBMC) in adult macaques. During their chronic asymptomatic phase of infection, the frequency of deleted proviral genomes was similar in PBMC and lymph nodes. The latter, however, harbored significantly more full-length proviral DNA than PBMC, consistent with the lack of effective antiviral cytotoxic T-cell activity in lymph nodes described by others during human immunodeficiency virus infection. After the macaques progressed to AIDS, full-length proviral DNA became equally abundant in lymph nodes and in PBMC. We have demonstrated that although a single molecular species of proviral DNA was inoculated, genomic diversity was detected within a short time, thus confirming the genetic instability of the SIV genome in vivo.
通过长距离DNA聚合酶链反应，我们前瞻性地追踪了经肌肉注射编码完整猴免疫缺陷病毒（SIV）的超螺旋质粒DNA的恒河猴。在接种后4至10周及之后，我们在成年猕猴的外周血单核细胞（PBMC）中检测到大量缺失的前病毒基因组以及全长病毒基因组。在其慢性无症状感染阶段，PBMC和淋巴结中缺失前病毒基因组的频率相似。然而，淋巴结中全长前病毒DNA的含量明显高于PBMC，这与其他人所描述的人类免疫缺陷病毒感染期间淋巴结中缺乏有效的抗病毒细胞毒性T细胞活性一致。猕猴发展为艾滋病后，全长前病毒DNA在淋巴结和PBMC中的含量变得同样丰富。我们已经证明，尽管接种的是单一分子种类的前病毒DNA，但在短时间内就检测到了基因组多样性，从而证实了SIV基因组在体内的遗传不稳定性。
