Harrington Patrick R, Connell Mary J, Meeker Rick B, Johnson Philip R, Swanstrom Ronald
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
J Infect Dis. 2007 Oct 1;196(7):1058-67. doi: 10.1086/520819. Epub 2007 Aug 29.
BACKGROUND. Human immunodeficiency virus (HIV) replication and compartmentalization in the central nervous system, including in cerebrospinal fluid (CSF), are associated with severe neurological disease and may contribute to viral persistence during antiretroviral therapy. To understand the relationships between viral populations in multiple compartments, we performed a systematic longitudinal characterization of viral populations in blood plasma and CSF obtained at short time intervals over the full course of infection in 3 macaques infected with simian immunodeficiency virus (SIVsm strain E660).
Complex viral genetic populations in blood plasma and CSF were characterized using a heteroduplex tracking assay targeted to the V1/V2 hypervariable region of env. To identify signs of neurological disease, monocyte chemoattractant protein (MCP)-1 levels in CSF and CD68(+) monocyte/macrophage infiltration in brain tissues were quantified.
Two patterns of blood/CSF viral dynamics were apparent as infection progressed: concordant blood/CSF viral evolution and discordant blood/CSF viral evolution. Perivascular CD68(+) cells in autopsy brain tissue and elevated CSF MCP-1 levels accompanied blood/CSF viral population discordance but not concordance.
Two distinct patterns of blood/CSF viral population dynamics can be observed in SIV-infected macaques, and the patterns may be associated with different neurological disease outcomes.
背景。人类免疫缺陷病毒（HIV）在中枢神经系统（包括脑脊液，CSF）中的复制和分隔与严重的神经疾病相关，并且可能在抗逆转录病毒治疗期间有助于病毒持续存在。为了了解多个区室中病毒群体之间的关系，我们对3只感染猿猴免疫缺陷病毒（SIVsm株E660）的猕猴在感染全过程中短时间间隔获取的血浆和CSF中的病毒群体进行了系统的纵向特征分析。
使用针对env基因V1/V2高变区的异源双链跟踪分析对血浆和CSF中的复杂病毒基因群体进行特征分析。为了确定神经疾病的迹象，对CSF中的单核细胞趋化蛋白（MCP）-1水平和脑组织中的CD68(+)单核细胞/巨噬细胞浸润进行了定量。
随着感染进展，出现了两种血浆/CSF病毒动力学模式：一致的血浆/CSF病毒进化和不一致的血浆/CSF病毒进化。尸检脑组织中的血管周围CD68(+)细胞和升高的CSF MCP-1水平伴随着血浆/CSF病毒群体的不一致而非一致。
在感染SIV的猕猴中可观察到两种不同的血浆/CSF病毒群体动力学模式，且这些模式可能与不同的神经疾病结局相关。
