Murray Jacinta, Fishman Sarah L, Ryan Elizabeth, Eng Francis J, Walewski José L, Branch Andrea D, Morgello Susan
Department of Pathology, Mount Sinai School of Medicine, New York, New York 10029, USA.
J Neurovirol. 2008 Jan;14(1):17-27. doi: 10.1080/13550280701708427.
Hepatitis C virus (HCV) has been detected in the brain tissues of 10 individuals reported to date; it is unclear what clinical factors are associated with this, and with what frequency it occurs. Accordingly, a pilot analysis utilizing reverse transcriptase-polymerase chain reaction (RT- PCR) to detect and sequence HCV in premortem plasma and postmortem brain and liver from 20 human immunodeficiency virus (HIV)-infected and 10 HIV-naive individuals was undertaken. RNA encoding the first 126 amino acids of the HCV E1 envelope protein and the majority of the E1 signal sequence was analyzed in parallel with an 80-base-long segment of the 5' untranslated region (UTR). Liver HCV was detected only in subjects with premortem HCV viremia (10 HIV-infected and 3 HIV-naive). Brain HCV was detected in 6/10 HCV/HIV-coinfected and 1/3 HCV-monoinfected subjects. In the setting of HIV, the magnitude of plasma HCV load did not correlate with the presence of brain HCV. However, coinfected patients with brain HCV were more often off antiretroviral therapy and tended to have higher plasma HIV loads than those with HCV restricted to liver. Furthermore, premortem cerebrospinal fluid (CSF) analysis revealed that HCV/HIV-coinfected patients with brain HCV had detectable CSF HIV, whereas those without brain HCV had undetectable CSF HIV loads (P = .0205). Neuropsychologic tests showed a trend for hierarchical impairment of abstraction/executive functioning in HIV/HCV coinfection, with mean T scores for HIV monoinfected patients 43.2 (7.3), for liver-only HCV 39.5 (9.0), and for those with HCV in brain and liver 33.2 (5.1) (P = .0927). Predominant brain HCV sequences did not match those of the plasma or liver in 4 of the 6 coinfected patients analyzed. We conclude that in the setting of HIV/HCV coinfection, brain HCV is a common phenomenon unrelated to the magnitude of HCV viremia, but related to active HIV disease and detectable CSF HIV. Furthermore, there is sequence evidence of brain compartmentalization. Differences in abstraction/executive function of HCV/HIV coinfected patients compared to HIV monoinfected warrant further studies to determine if neuropsychiatric effects are predicated upon brain infection.
据报道，迄今为止在10名个体的脑组织中检测到丙型肝炎病毒（HCV）；目前尚不清楚哪些临床因素与之相关，以及其发生频率如何。因此，开展了一项初步分析，利用逆转录聚合酶链反应（RT-PCR）检测20名感染人类免疫缺陷病毒（HIV）者和10名未感染HIV者生前血浆、死后脑和肝组织中的HCV并进行测序。对编码HCV E1包膜蛋白前126个氨基酸的RNA以及E1信号序列的大部分与5'非翻译区（UTR）的一个80个碱基长的片段进行了平行分析。仅在生前有HCV病毒血症的受试者中检测到肝内HCV（10名HIV感染者和3名未感染HIV者）。在6/10的HCV/HIV合并感染者和1/3的HCV单一感染者中检测到脑内HCV。在HIV感染情况下，血浆HCV载量与脑内HCV的存在无关。然而，脑内有HCV的合并感染患者比HCV仅局限于肝脏的患者更常停用抗逆转录病毒治疗，且血浆HIV载量往往更高。此外，生前脑脊液（CSF）分析显示，脑内有HCV的HCV/HIV合并感染患者的脑脊液中可检测到HIV，而脑内无HCV的患者脑脊液中HIV载量不可检测（P = 0.0205）。神经心理学测试显示，HIV/HCV合并感染患者在抽象/执行功能方面有分层损害的趋势，HIV单一感染患者的平均T分数为43.2（7.3），仅肝脏有HCV的患者为39.5（9.0），脑和肝脏均有HCV的患者为33.2（5.1）（P = 0.0927）。在分析的6名合并感染患者中，有4名患者脑内主要的HCV序列与血浆或肝脏的序列不匹配。我们得出结论，在HIV/HCV合并感染的情况下，脑内HCV是一种常见现象，与HCV病毒血症的程度无关，但与活跃的HIV疾病和可检测到的脑脊液HIV有关。此外，有序列证据表明存在脑内分隔。与HIV单一感染相比，HCV/HIV合并感染患者在抽象/执行功能方面的差异值得进一步研究，以确定神经精神效应是否基于脑感染。
