Alterations in the levels of vesicular trafficking proteins involved in HIV replication in the brains and CSF of patients with HIV-associated neurocognitive disorders.
Alterations in the levels of vesicular trafficking proteins involved in HIV replication in the brains and CSF of patients with HIV-associated neurocognitive disorders.
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DOI：
10.1007/s11481-013-9511-3
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发表时间：
2013-12
影响因子：
6.2
通讯作者：
Masliah, Eliezer
中科院分区：
文献类型：
--
作者：
Fields, Jerel;Dumaop, Wilmar;Adame, Anthony;Ellis, Ronald J.;Letendre, Scott;Grant, Igor;Masliah, Eliezer
尽管抗逆转录病毒疗法有所改进，但人类免疫缺陷病毒 (HIV) 相关的神经认知障碍 (HAND) 仍然普遍存在。指示神经心理损伤（NPI）的 HAND 特异性生物标志物将有助于深入了解疾病进展并帮助临床医生设计治疗方法。转运所需的内体分选复合物 (ESCRT) 蛋白，如肿瘤易感基因 (TSG)-101、液泡蛋白分选 (VPS)-4 和 LIP-5 对于 HIV 复制很重要，最近抗病毒干扰素刺激基因 (ISG)-15 被提议作为中枢神经系统损伤的生物标志物。在这里，我们分析了一组经过充分表征的 HIV+ 脑脊液 (CSF) 和死后脑样本，以了解多种囊泡运输蛋白和相关的先天免疫蛋白 ISG-15、TSG-101、VPS-4 和 LIP-5。随着 NPI 和神经病理学的增加，所有蛋白质水平均呈上升趋势。与正常病例相比，HIV 脑炎 (HIVE) 患者的 ISG-15 CSF 水平升高，四分之三的 HIVE 样本的 CSF ISG-15 水平高于平均水平。与正常患者相比，NPI/NPI-O 患者的 VPS-4 CSF 水平升高。 HIV 相关痴呆患者的 VPS-4 CSF 水平与正常患者相当。 LIP-5 CSF 水平与 ISG-15 水平呈正相关，高于平均 ISG-15 水平表明病毒载量升高。免疫印迹和免疫组织化学分析显示神经元细胞体和星形胶质细胞中 ISG-15、VPS-4 和 LIP-5 的表达增加。结合病毒载量分析的 ESCRT 蛋白 CSF 水平可能指示 NPI 阶段，并可能有助于 HIV 患者的诊断和治疗设计。对 HIV 感染期间 ESCRT 蛋白表达的进一步研究可能会产生一个有前景的生物标志物，用于预测 NPI 的进展。
Human immunodeficiency virus (HIV) associated neurocognitive disorders (HAND) remain prevalent despite improved antiretroviral therapies. A HAND-specific biomarker indicative of neuropsychological impairment (NPI) would give insight into disease progression and aid clinicians in designing therapy. Endosomal sorting complex required for transport (ESCRT) proteins such as tumor susceptibility gene (TSG)-101, vacuolar protein sorting (VPS)-4 and LIP-5 are important for HIV replication and recently antiviral interferon stimulated gene (ISG)-15 was proposed as a biomarker for CNS injury. Here, we analyzed a well-characterized cohort of HIV+ cerebral spinal fluid (CSF) and postmortem brain specimens for multiple vesicular trafficking proteins and a related innate immune protein, ISG-15, TSG-101, VPS-4 and LIP-5. All protein levels trended higher with increased NPI and neuropathology. ISG-15 CSF levels were increased in HIV encephalitis (HIVE) compared to normal cases, and three quarters of HIVE samples had above average CSF ISG-15 levels. VPS-4 CSF levels were increased in NPI/NPI-O compared to normal patients. VPS-4 CSF levels in HIV-associated dementia were equivalent to that of normal patients. LIP-5 CSF levels positively correlate with ISG-15 levels, and higher than average ISG-15 levels indicate elevated viral load. Immunoblot and immunohistochemical analyses show increased expression of ISG-15, VPS-4 and LIP-5 in neuronal cell bodies and astroglial cells. ESCRT protein CSF levels analyzed in conjunction with viral load may be indicative of NPI stage, and may aid in the diagnosis and design of therapies for HIV patients. Further studies on the ESCRT protein expression during HIV infection may lead to a promising biomarker for predicting progression of NPI.
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影响因子：
3.2
作者：
Heaton, Robert K.;Franklin, Donald R.;Ellis, Ronald J.;McCutchan, J. Allen;Letendre, Scott L.;LeBlanc, Shannon;Corkran, Stephanie H.;Duarte, Nichole A.;Clifford, David B.;Woods, Steven P.;Collier, Ann C.;Marra, Christina M.;Morgello, Susan;Mindt, Monica Rivera;Taylor, Michael J.;Marcotte, Thomas D.;Atkinson, J. Hampton;Wolfson, Tanya;Gelman, Benjamin B.;McArthur, Justin C.;Simpson, David M.;Abramson, Ian;Gamst, Anthony;Fennema-Notestine, Christine;Jernigan, Terry L.;Wong, Joseph;Grant, Igor
通讯作者：
Grant, Igor
影响因子：
3.7
作者：
Gerena, Yamil;Skolasky, Richard L.;Wojna, Valerie
通讯作者：
Wojna, Valerie
DOI：
10.1097/00126334-200309011-00013
发表时间：
2003-09-01
影响因子：
3.6
作者：
Montaner, JSG;Côté, HCF;O'Shaughnessy, MV
通讯作者：
O'Shaughnessy, MV
影响因子：
6.3
作者：
Nakka, Venkata P.;Lang, Bradley T.;Vemuganti, Raghu
通讯作者：
Vemuganti, Raghu
影响因子：
3.3
作者：
Everall, I;Salaria, S;Masliah, E
通讯作者：
Masliah, E