Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA.
Curr Opin HIV AIDS. 2012 Jan;7(1):71-8. doi: 10.1097/COH.0b013e32834dde01.
A key factor driving AIDS-associated immunopathogenesis is chronic immune activation. Simian immunodeficiency virus (SIV) infection of African natural host species leads to high viremia, but low immune activation and absence of disease. Considerable progress in our understanding of pathological immune activation has come from comparative studies of SIV infection in pathogenic Asian macaque species and natural hosts. The focus of this review is to highlight recent work on the natural host model using high-throughput genomics.
Several groups have independently conducted microarray gene expression profiling comparing in-vivo SIV infection in natural and non-natural hosts. A consistent finding between these studies is that both pathogenic SIV infection of macaques and nonpathogenic infections of natural hosts have strong induction of interferon-stimulated genes (ISGs) early on, but a key difference was that natural hosts down-modulated the interferon response rapidly after acute infection. The development of new genome-based resources for further study of the natural host model is discussed.
Initial efforts using high-throughput biology to study SIV infection of natural hosts have effectively identified the ability of natural hosts to resolve interferon responses and immune activation. Further application of 'omic-based technologies coupled with integrative systems-based analysis should continue to yield progress.
导致艾滋病相关免疫发病机制的一个关键因素是慢性免疫激活。非洲自然宿主物种中的猴免疫缺陷病毒（SIV）感染会导致高病毒血症，但免疫激活水平低，且不会发病。我们对 SIV 感染致病性亚洲猕猴物种和自然宿主的病理免疫激活的理解有了相当大的进展。本综述的重点是强调使用高通量基因组学的自然宿主模型的最新研究。
几个小组独立进行了比较体内 SIV 在自然和非自然宿主中的感染的基因表达谱微阵列分析。这些研究之间的一个一致发现是，致病性猕猴 SIV 感染和自然宿主的非致病性感染都在早期强烈诱导干扰素刺激基因（ISGs），但一个关键区别是自然宿主在急性感染后迅速下调干扰素反应。讨论了用于进一步研究自然宿主模型的新基因组资源的发展。
使用高通量生物学研究自然宿主 SIV 感染的初步努力有效地确定了自然宿主能够解决干扰素反应和免疫激活的能力。进一步应用“组学”技术加上整合系统分析应该会继续取得进展。
