Chakrabarti Lisa A
Viral Immunology Unit, Pasteur Institute, 28 rue du Dr. Roux, 75724 Paris Cedex 15, France.
Front Biosci. 2004 Jan 1;9:521-39. doi: 10.2741/1123.
Simian immunodeficiency virus SIVsm causes an asymptomatic infection in its natural host, the sooty mangabey, but induces an immunodeficiency syndrome very similar to human AIDS when transferred to a new host species such as the rhesus macaque. Unexpectedly, SIVsm replication dynamics is comparable in the two species, with rapid accumulation of viral mutations and a high viral load detected in both mangabeys and macaques. In contrast, clear differences are observed in immune parameters. Pathogenic SIV infection in macaques is associated with decreased CD4+ T cell numbers and signs of generalized immune activation, such as increased numbers of cycling and apoptotic T cells, hyperplasic lymphoid tissues, and exacerbated immune responses. Mangabeys with asymptomatic SIV infection show normal T cell regeneration parameters and signs of a moderate immune response, appropriate in the setting of chronic viral infection. The comparative analysis of simian models thus suggests that viral load alone cannot account for progression to disease, and that the capacity of primate lentiviruses to induce abnormal immune activation underlies AIDS pathogenesis.
猴免疫缺陷病毒SIVsm在其天然宿主乌黑白眉猴中引起无症状感染，但当转移到新宿主物种如恒河猴时，会引发一种与人类艾滋病非常相似的免疫缺陷综合征。出乎意料的是，SIVsm在这两个物种中的复制动态相当，在白眉猴和恒河猴中都检测到病毒突变的快速积累和高病毒载量。相比之下，在免疫参数方面观察到明显差异。恒河猴中致病性SIV感染与CD4 + T细胞数量减少以及全身免疫激活的迹象有关，如循环和凋亡T细胞数量增加、淋巴组织增生以及免疫反应加剧。无症状SIV感染的白眉猴表现出正常的T细胞再生参数和适度免疫反应的迹象，这在慢性病毒感染的情况下是适当的。因此，对猴模型的比较分析表明，仅病毒载量不能解释疾病的进展，灵长类慢病毒诱导异常免疫激活的能力是艾滋病发病机制的基础。
