Bissel Stephanie J, Wang Guoji, Bonneh-Barkay Dafna, Starkey Adam, Trichel Anita M, Murphey-Corb Michael, Wiley Clayton A
Department of Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA.
J Virol. 2008 May;82(10):5031-42. doi: 10.1128/JVI.02069-07. Epub 2008 Mar 12.
The brains of individuals with lentiviral-associated encephalitis contain an abundance of infected and activated macrophages. It has been hypothesized that encephalitis develops when increased numbers of infected monocytes traffic into the central nervous system (CNS) during the end stages of immunosuppression. The relationships between the infection of brain and systemic macrophages and circulating monocytes and the development of lentiviral encephalitis are unknown. We longitudinally examined the extent of monocyte/macrophage infection in blood and lymph nodes of pigtailed macaques that did or did not develop simian immunodeficiency virus encephalitis (SIVE). Compared to levels in macaques that did not develop SIVE, more ex vivo virus production was detected from monocyte-derived macrophages and nonadherent peripheral blood mononuclear cells (PBMCs) from macaques that did develop SIVE. Prior to death, there was an increase in the number of circulating PBMCs following a rise in cerebrospinal fluid viral load in macaques that did develop SIVE but not in nonencephalitic macaques. At necropsy, macaques with SIVE had more infected macrophages in peripheral organs, with the exception of lymph nodes. T cells and NK cells with cytotoxic potential were more abundant in brains with encephalitis; however, T-cell and NK-cell infiltration in SIVE and human immunodeficiency virus encephalitis was more modest than that observed in classical acute herpes simplex virus encephalitis. These findings support the hypothesis that inherent differences in host systemic and CNS monocyte/macrophage viral production are associated with the development of encephalitis.
患有慢病毒相关性脑炎的个体大脑中含有大量被感染并激活的巨噬细胞。据推测，在免疫抑制末期，当进入中枢神经系统（CNS）的被感染单核细胞数量增加时，脑炎就会发生。脑巨噬细胞和全身巨噬细胞以及循环单核细胞的感染与慢病毒脑炎的发展之间的关系尚不清楚。我们纵向检测了患或未患猴免疫缺陷病毒脑炎（SIVE）的猪尾猕猴血液和淋巴结中单核细胞/巨噬细胞的感染程度。与未患SIVE的猕猴相比，从患SIVE的猕猴的单核细胞衍生巨噬细胞和非贴壁外周血单核细胞（PBMC）中检测到更多的体外病毒产生。在死亡前，患SIVE的猕猴脑脊液病毒载量上升后，循环PBMC数量增加，而非脑炎猕猴则没有。尸检时，除淋巴结外，患SIVE的猕猴外周器官中有更多被感染的巨噬细胞。具有细胞毒性潜能的T细胞和NK细胞在患有脑炎的大脑中更为丰富；然而，SIVE和人类免疫缺陷病毒脑炎中的T细胞和NK细胞浸润比经典急性单纯疱疹病毒脑炎中观察到的要温和。这些发现支持了宿主全身和中枢神经系统单核细胞/巨噬细胞病毒产生的内在差异与脑炎发展相关的假说。
