Ling Binhua, Apetrei Cristian, Pandrea Ivona, Veazey Ronald S, Lackner Andrew A, Gormus Bobby, Marx Preston A
Tulane National Primate Research Center, 18703 Three Rivers Rd., Covington, LA 70433, USA.
J Virol. 2004 Aug;78(16):8902-8. doi: 10.1128/JVI.78.16.8902-8908.2004.
Prevailing theory holds that simian immunodeficiency virus (SIV) infections are nonpathogenic in their natural simian hosts and that lifelong infections persist without disease. Numerous studies have reported that SIV-infected sooty mangabeys (SMs; Cercocebus atys) remain disease free for up to 24 years despite relatively high levels of viral replication. Here, we report that classic AIDS developed after an 18-year incubation in an SM (E041) with a natural SIVsm infection. Unlike that described in previous reports of SIV-related disease in SMs, the SIVsm infecting E041 was not first passaged through macaques; moreover, SM E041 was simian T-cell leukemia virus antibody negative. SM E041 was euthanized in 2002 after being diagnosed with severe disseminated B-cell lymphoma. The plasma virus load had been approximately the same for 16 years when a 100-fold increase in virus load occurred in years 17 and 18. Additional findings associated with AIDS were CD4(+)-cell decline, loss of p27 core antibody, and loss of control of SIVsm replication with disseminated giant cell disease. These findings suggest that the time to development of AIDS exceeds the average lifetime of SMs in the wild and that the principal adaptation of SIV to its natural African hosts does not include complete resistance to disease. Instead, AIDS may develop slowly, even in the presence of high virus loads. However, a long-term relatively high virus load, such as that in SM E041, is consistent with AIDS development in less than 18 years in humans and macaques. Therefore, the results also suggest that SMs have a special mechanism for resisting AIDS development.
流行理论认为,猿猴免疫缺陷病毒(SIV)感染在其自然猿猴宿主中不具有致病性,终身感染持续存在且无疾病发生。大量研究报告称,感染SIV的乌黑白眉猴(SMs;Cercocebus atys)尽管病毒复制水平相对较高,但在长达24年的时间里仍未发病。在此,我们报告一只自然感染SIVsm的SM(E041)在潜伏18年后发展为典型的艾滋病。与之前关于SMs中SIV相关疾病的报道不同,感染E041的SIVsm并未先在猕猴中传代;此外,SM E041的猿猴T细胞白血病病毒抗体呈阴性。SM E041在被诊断出患有严重播散性B细胞淋巴瘤后于2002年实施安乐死。在第17年和第18年病毒载量增加100倍之前,血浆病毒载量在16年里大致相同。与艾滋病相关的其他发现包括CD4(+)细胞减少、p27核心抗体丧失以及SIVsm复制失控并伴有播散性巨细胞疾病。这些发现表明,艾滋病的发展时间超过了野生SMs的平均寿命,并且SIV对其天然非洲宿主的主要适应性不包括对疾病的完全抗性。相反,艾滋病可能发展缓慢,即使在病毒载量较高的情况下也是如此。然而,长期相对较高的病毒载量,如SM E041中的情况,与人类和猕猴在不到18年的时间里发展为艾滋病是一致的。因此,研究结果还表明,SMs具有抵抗艾滋病发展的特殊机制。