Center for Vaccine Research, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
PLoS Pathog. 2013 Jan;9(1):e1003011. doi: 10.1371/journal.ppat.1003011. Epub 2013 Jan 17.
Pathogenesis studies of SIV infection have not been performed to date in wild monkeys due to difficulty in collecting and storing samples on site and the lack of analytical reagents covering the extensive SIV diversity. We performed a large scale study of molecular epidemiology and natural history of SIVagm infection in 225 free-ranging AGMs from multiple locations in South Africa. SIV prevalence (established by sequencing pol, env, and gag) varied dramatically between infant/juvenile (7%) and adult animals (68%) (p<0.0001), and between adult females (78%) and males (57%). Phylogenetic analyses revealed an extensive genetic diversity, including frequent recombination events. Some AGMs harbored epidemiologically linked viruses. Viruses infecting AGMs in the Free State, which are separated from those on the coastal side by the Drakensberg Mountains, formed a separate cluster in the phylogenetic trees; this observation supports a long standing presence of SIV in AGMs, at least from the time of their speciation to their Plio-Pleistocene migration. Specific primers/probes were synthesized based on the pol sequence data and viral loads (VLs) were quantified. VLs were of 10(4)-10(6) RNA copies/ml, in the range of those observed in experimentally-infected monkeys, validating the experimental approaches in natural hosts. VLs were significantly higher (10(7)-10(8) RNA copies/ml) in 10 AGMs diagnosed as acutely infected based on SIV seronegativity (Fiebig II), which suggests a very active transmission of SIVagm in the wild. Neither cytokine levels (as biomarkers of immune activation) nor sCD14 levels (a biomarker of microbial translocation) were different between SIV-infected and SIV-uninfected monkeys. This complex algorithm combining sequencing and phylogeny, VL quantification, serology, and testing of surrogate markers of microbial translocation and immune activation permits a systematic investigation of the epidemiology, viral diversity and natural history of SIV infection in wild African natural hosts.
迄今为止，由于难以在现场采集和储存样本，以及缺乏涵盖广泛 SIV 多样性的分析试剂，因此尚未对野生猴子中的 SIV 感染发病机制进行研究。我们对来自南非多个地点的 225 只自由放养的 AGS 进行了大规模的 SIVagm 感染的分子流行病学和自然史研究。通过对 pol、env 和 gag 进行测序来确定 SIV 的流行率（以下简称“流行率”）在婴儿/青少年（7%）和成年动物（68%）之间存在显著差异（p<0.0001），在成年雌性（78%）和雄性（57%）之间也存在显著差异。系统发育分析显示出广泛的遗传多样性，包括频繁的重组事件。一些 AGS 携带具有流行病学联系的病毒。在自由州感染 AGS 的病毒与沿海地区的病毒在德拉肯斯堡山脉隔开，在系统发育树中形成了一个单独的聚类；这一观察结果支持 SIV 在 AGS 中存在很长时间，至少从它们分化到上新世-更新世的迁徙以来就存在。根据 pol 序列数据合成了特异性引物/探针，并定量了病毒载量（VL）。VL 为 10(4)-10(6) RNA 拷贝/ml，与实验感染猴子中观察到的 VL 范围一致，验证了在自然宿主中进行的实验方法。根据 SIV 血清阴性（Fiebig II）诊断为急性感染的 10 只 AGS 的 VL 显著更高（10(7)-10(8) RNA 拷贝/ml），这表明 SIVagm 在野外的传播非常活跃。感染 SIV 的猴子与未感染 SIV 的猴子之间的细胞因子水平（作为免疫激活的生物标志物）和 sCD14 水平（微生物易位的生物标志物）没有差异。这种结合了测序和系统发育、VL 定量、血清学以及微生物易位和免疫激活的替代标志物检测的复杂算法，允许对野生非洲自然宿主中的 SIV 感染的流行病学、病毒多样性和自然史进行系统研究。
