Unit of Infectious Diseases, Department of Medical Sciences, University of Torino.
Laboratory of Virology and Molecular Biology, Ospedale Amedeo di Savoia, ASL 'Città di Torino'.
AIDS. 2020 Mar 1;34(3):373-380. doi: 10.1097/QAD.0000000000002442.
The current study aimed to investigate whether cerebrospinal fluid (CSF) Epstein-Barr virus (EBV) or cytomegalovirus (CMV) DNA was associated with viral, inflammatory and neuronal damage biomarkers in people living with HIV (PLWH).
A cross-sectional diagnostic study on CSF fluid samples in patients undergoing lumbar punctures for clinical reasons, to better understand the role of EBV and CMV in the CNS on HIV RNA replication, blood-brain-barrier (BBB) damage and biomarkers of neuronal damage/inflammation.
EBV, CMV DNA and HIV RNA were measured on CSF, through real time (RT)-PCR, from PLWHs undergoing lumbar punctures for clinical reasons (excluding oncho-haematological comorbidities). Immune-enzymatic assays evaluated blood-brain barrier inflammation and damage. Patients were stratified according to plasma HIV RNA levels in viremic (≥50 copies/ml) and aviremic (<50 copies/ml).
We included 297 participants. Among 167 viremic patients CSF EBV and CMV DNA were detectable in 42 (25.1%) and 10 (6.3%) participants; among 130 aviremic individuals CSF EBV and CMV DNA were detectable in 12 (9.2%) and 0 (0%) participants, respectively. In viremic group detectable CSF EBV DNA was associated with CSF pleocytosis (P < 0.001), higher CSF HIV RNA (P < 0.001) and neopterin levels (P = 0.002). In aviremic participants detectable EBV DNA was associated with pleocytosis (P = 0.056), higher neopterin (P = 0.027) and immune globulins (P = 0.016) in the CSF; CSF escape was more common in those with detectable EBV DNA (50 vs. 21.2%, P = 0.036).
EBV DNA was frequently detected in the CSF of viremic and fewer aviremic patients on antiretroviral treatment. In PLWH without clinical evidence of encephalitis CSF EBV DNA was associated with higher biomarkers levels of neuronal damage/inflammation. The role of EBV reactivation in HIV-associated central nervous system disorders warrants further studies.
本研究旨在探讨脑脊液（CSF）中 Epstein-Barr 病毒（EBV）或巨细胞病毒（CMV）DNA 是否与 HIV 感染者（PLWH）的病毒、炎症和神经元损伤生物标志物相关。
一项针对因临床原因接受腰椎穿刺的患者 CSF 液样本的横断面诊断研究，旨在更好地了解 EBV 和 CMV 在 HIV RNA 复制、血脑屏障（BBB）损伤和神经元损伤/炎症的生物标志物中的中枢神经系统作用。
通过实时（RT）-PCR 检测 CSF 中的 EBV、CMV DNA 和 HIV RNA，这些患者因临床原因（不包括血液学合并症）接受腰椎穿刺。免疫酶联测定评估血脑屏障炎症和损伤。根据血浆 HIV RNA 水平将患者分为病毒血症（≥50 拷贝/ml）和非病毒血症（<50 拷贝/ml）。
我们纳入了 297 名参与者。在 167 名病毒血症患者中，CSF EBV 和 CMV DNA 可检测到 42 名（25.1%）和 10 名（6.3%）患者；在 130 名非病毒血症患者中，CSF EBV 和 CMV DNA 可检测到 12 名（9.2%）和 0 名（0%）患者。在病毒血症组中，可检测到的 CSF EBV DNA 与 CSF 白细胞增多（P<0.001）、更高的 CSF HIV RNA（P<0.001）和新蝶呤水平（P=0.002）相关。在非病毒血症参与者中，可检测到的 EBV DNA 与白细胞增多（P=0.056）、更高的新蝶呤（P=0.027）和免疫球蛋白（P=0.016）相关；在可检测到 EBV DNA 的患者中，CSF 逃逸更为常见（50%比 21.2%，P=0.036）。
在接受抗逆转录病毒治疗的病毒血症和较少的非病毒血症患者中，CSF 中 EBV DNA 经常被检测到。在没有临床证据的 HIV 相关脑炎的 PLWH 中，CSF EBV DNA 与更高的神经元损伤/炎症生物标志物水平相关。EBV 再激活在 HIV 相关中枢神经系统疾病中的作用值得进一步研究。
