Dynamics of simian immunodeficiency virus Populations in blood and cerebrospinal fluid over the full course of infection
Dynamics of simian immunodeficiency virus Populations in blood and cerebrospinal fluid over the full course of infection
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DOI：
10.1086/520819
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发表时间：
2007-10-01
影响因子：
6.4
通讯作者：
Swanstrom, Ronald
中科院分区：
文献类型：
--
作者：
Harrington, Patrick R.;Connell, Mary J.;Swanstrom, Ronald
背景人类免疫缺陷病毒（HIV）在中枢神经系统（包括脑脊液（CSF））中的复制和区室化与严重的神经系统疾病相关，并可能导致抗逆转录病毒治疗期间的病毒持续存在。为了了解病毒种群之间的关系，在多个隔室，我们进行了系统的纵向表征的病毒种群在血浆和CSF中获得在短时间间隔在整个过程中感染猴免疫缺陷病毒（SIVsm株E660）。血浆和CSF中的复杂病毒遗传群体使用靶向env的V1/V2高变区的异源双链追踪测定来表征。为了识别神经系统疾病的体征，定量CSF中单核细胞趋化蛋白（MCP）-1水平和脑组织中CD 68（+）单核细胞/巨噬细胞浸润。随着感染进展，血液/CSF病毒动力学的两种模式明显：一致的血液/CSF病毒演变和不一致的血液/CSF病毒演变。尸检脑组织中血管周围CD 68+细胞和CSF MCP-1水平升高伴随血液/CSF病毒群不一致但不一致。在SIV感染的猕猴中可以观察到两种不同的血液/CSF病毒群体动力学模式，并且这些模式可能与不同的神经系统疾病结局相关。
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).Methods. 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.Results. 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.Conclusions. 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.