Bissel Stephanie J, Wang Guoji, Trichel Anita M, Murphey-Corb Michael, Wiley Clayton A
Department of Infectious Diseases and Microbiology, Graduate School of Public Health, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Am J Pathol. 2006 May;168(5):1553-69. doi: 10.2353/ajpath.2006.050240.
The histopathological hallmark of lentiviral-associated encephalitis is an abundance of infected and activated macrophages. Why a subset of infected hosts develops lentiviral encephalitis and others do not is unknown. Using a CD8(+) T-cell depletion model of simian immunodeficiency virus (SIV)-infected rhesus macaques, we examined the relationship between peripheral SIV infection of monocytes/macrophages and the development of encephalitis. At the same time that cerebral spinal fluid viral load increased in macaques that developed encephalitis, we observed that monocyte-derived macrophages from these macaques produced more virus than those from macaques that did not develop encephalitis. However, during the course of infection, the number of blood monocyte-associated SIV DNA copies did not distinguish macaques that developed simian immunodeficiency virus encephalitis from macaques that did not develop encephalitis. Paradoxically, in this model, macaques that developed encephalitis had fewer SIV-infected macrophages in lungs and thymus at postmortem than macaques that did not develop encephalitis. These findings suggest that inherent differences in host monocyte viral production are related to development of encephalitis.
慢病毒相关脑炎的组织病理学特征是存在大量被感染并激活的巨噬细胞。为何一部分受感染宿主会发展为慢病毒脑炎而其他宿主不会，目前尚不清楚。我们利用感染了猿猴免疫缺陷病毒（SIV）的恒河猴的CD8(+) T细胞耗竭模型，研究了外周血单核细胞/巨噬细胞的SIV感染与脑炎发展之间的关系。在发展为脑炎的猕猴脑脊液病毒载量增加的同时，我们观察到这些猕猴的单核细胞衍生巨噬细胞比未发展为脑炎的猕猴的巨噬细胞产生更多病毒。然而，在感染过程中，血液中与单核细胞相关的SIV DNA拷贝数并不能区分出发展为猿猴免疫缺陷病毒脑炎的猕猴和未发展为脑炎的猕猴。矛盾的是，在这个模型中，发展为脑炎的猕猴在死后肺和胸腺中被SIV感染的巨噬细胞比未发展为脑炎的猕猴少。这些发现表明，宿主单核细胞病毒产生的内在差异与脑炎的发展有关。
