Greenwood Edward J D, Schmidt Fabian, Kondova Ivanela, Niphuis Henk, Hodara Vida L, Clissold Leah, McLay Kirsten, Guerra Bernadette, Redrobe Sharon, Giavedoni Luis D, Lanford Robert E, Murthy Krishna K, Rouet François, Heeney Jonathan L
Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom.
Division of Pathology and Microbiology, Biomedical Primate Research Centre, Rijswijk, The Netherlands.
PLoS Pathog. 2015 Sep 11;11(9):e1005146. doi: 10.1371/journal.ppat.1005146. eCollection 2015 Sep.
The virus-host relationship in simian immunodeficiency virus (SIV) infected chimpanzees is thought to be different from that found in other SIV infected African primates. However, studies of captive SIVcpz infected chimpanzees are limited. Previously, the natural SIVcpz infection of one chimpanzee, and the experimental infection of six chimpanzees was reported, with limited follow-up. Here, we present a long-term study of these seven animals, with a retrospective re-examination of the early stages of infection. The only clinical signs consistent with AIDS or AIDS associated disease was thrombocytopenia in two cases, associated with the development of anti-platelet antibodies. However, compared to uninfected and HIV-1 infected animals, SIVcpz infected animals had significantly lower levels of peripheral blood CD4+ T-cells. Despite this, levels of T-cell activation in chronic infection were not significantly elevated. In addition, while plasma levels of β2 microglobulin, neopterin and soluble TNF-related apoptosis inducing ligand (sTRAIL) were elevated in acute infection, these markers returned to near-normal levels in chronic infection, reminiscent of immune activation patterns in 'natural host' species. Furthermore, plasma soluble CD14 was not elevated in chronic infection. However, examination of the secondary lymphoid environment revealed persistent changes to the lymphoid structure, including follicular hyperplasia in SIVcpz infected animals. In addition, both SIV and HIV-1 infected chimpanzees showed increased levels of deposition of collagen and increased levels of Mx1 expression in the T-cell zones of the lymph node. The outcome of SIVcpz infection of captive chimpanzees therefore shares features of both non-pathogenic and pathogenic lentivirus infections.
人们认为，感染猿猴免疫缺陷病毒（SIV）的黑猩猩体内的病毒-宿主关系与其他感染SIV的非洲灵长类动物不同。然而，对圈养的感染SIVcpz的黑猩猩的研究有限。此前，曾报道过一只黑猩猩的自然SIVcpz感染以及六只黑猩猩的实验性感染，但随访有限。在此，我们对这七只动物进行了长期研究，并对感染早期阶段进行了回顾性重新检查。与艾滋病或艾滋病相关疾病一致的唯一临床症状是两例血小板减少症，与抗血小板抗体的产生有关。然而，与未感染和感染HIV-1的动物相比，感染SIVcpz的动物外周血CD4+T细胞水平显著较低。尽管如此，慢性感染时T细胞活化水平并未显著升高。此外，虽然在急性感染时血浆β2微球蛋白、新蝶呤和可溶性肿瘤坏死因子相关凋亡诱导配体（sTRAIL）水平升高，但这些标志物在慢性感染时恢复到接近正常水平，这让人联想到“自然宿主”物种中的免疫激活模式。此外，慢性感染时血浆可溶性CD14未升高。然而，对二级淋巴组织环境的检查发现淋巴结构持续发生变化，包括感染SIVcpz的动物出现滤泡增生。因此，圈养黑猩猩感染SIVcpz的结果兼具非致病性和致病性慢病毒感染的特征。
