Presence of Epstein–Barr virus DNA in cerebrospinal fluid is associated with greater HIV RNA and inflammation

Abstract

Epstein-Barr virus (EBV) and Cytomegalovirus (CMV) can infect several cells, replicate in the 48 central nervous system and affect blood-brain barrier (BBB) integrity. This study aimed to 49 investigate whether cerebrospinal fluid (CSF) EBV or CMV DNA was associated with viral, 50 inflammatory and neuronal damage biomarkers in people living with HIV (PLWH). 51 EBV, CMV DNA and HIV RNA were measured on CSF, through RT-PCR, from PLWHs 52 undergoing lumbar punctures for clinical reasons (excluding oncho-haematological 53 comorbidities). Immune-enzymatic assays evaluated BBB inflammation and damage. Patients 54 were stratified according to plasma HIV RNA levels in viremic (≥50 copies/mL) and aviremic 55 (<50 copies/mL). We included 298 participants. Among 167 viremic patients CSF EBV and 56 CMV DNA were detectable in 42 (25.1%) and 10 (6.3%) participants; among 130 aviremic 57 subjects CSF EBV and CMV DNA were detectable in 12 (9.2%) and 0 (0%) participants, 58 respectively. In viremic group detectable CSF EBV DNA was associated with CSF pleocytosis 59 (p<0.001), higher CSF HIV RNA (p<0.001) and neopterin levels (p=0.002). In aviremic 60 participants detectable EBV DNA was associated with pleocytosis (p=0.056), higher neopterin 61 (p=0.027) and immune globulins (p=0.016) in the CSF; CSF escape was more common in those 62 with detectable EBV DNA (50% vs 21.2%, p=0.036). 63 EBV DNA was frequently detected in the CSF of viremic and fewer aviremic patients on 64 antiretroviral treatment. In PLWH without clinical evidence of encephalitis CSF EBV DNA was 65 associated with higher levels of HIV RNA and biomarkers of neuronal damage/inflammation. 66The role of EBV reactivation in HIV-associated CNS disorders warrants further studies. 67 68 ha eliminato: 69 ha eliminato: The aim of this study was 70 ha eliminato: We examined CSF samples participants 71 undergoing lumbar punctures for clinical reasons 72

Blood–Brain Barrier Impairment in Patients Living with HIV: Predictors and Associated Biomarkers

“…EBV infects more than 90% of the worldwide population and it is associated with several cancers in PLWH, including Hodgkin lymphomas, non-Hodgkin lymphomas and Burkitt lymphomas [ 33 ]. Dehee and colleagues found a similar rate of EBV detection among 227 HIV-positive subjects and controls [ 34 ], but higher viral loads in the former ones: despite EBV replication may just represent a less controlling immune system studying EBV may be useful for understanding chronic immune activation and some HIV-associated non-infectious comorbidities [ 35 ].…”

Impact of the Film Array Meningitis/Encephalitis panel in adults with meningitis and encephalitis in Colombia

“…Given the severity of the outcomes that may result from stopping an antifungal therapy due to a false-negative FAME panel, it is recommended that if the clinical suspicion of cryptococcosis is high not to discontinue antifungal therapy until a CSF cryptococcal latex antigen is obtained or the CSF culture is finalised [8]. The panel does not identify Epstein–Barr Virus (EBV), which has been related with neuronal inflammation, endothelial damage (even in the absence of clinical encephalitis) and central nervous system lymphoma in immunosuppressed patients, with impact in the development of cognitive dysfunction and psychiatric symptoms [14]. EBV is also associated with post-transplant lymphoproliferative disorder and occasionally with encephalitis in solid organ transplant patients' recipients [15].…”

Epstein-Barr Virus and Neurological Diseases

“…However, cytotoxic CD4 + activated memory T-cells in the CNS are associated with elevated PD-L1 expression. Further, EBV can suppress CNS immune responses by expressing viral proteins with immune evasion function (e.g, EBNA1, LMP1, LMP2A), thereby maintaining T-cell-mediated inflammatory responses and inducing the development of EBV encephalitis ( Figure 1E ) ( Johnson et al, 2019 ; Lupia et al, 2020 ).…”

“…In B cells, virus lytic replication can occur during latency reactivation, and the transition from latency to the lytic cycle is mediated by BZLF1 and BRLF1 viral proteins that trigger the expression of certain viral genes (e.g., BCRF1, BHRF1) and down-regulate the host immune response, which ultimately leads to cell death and the release of viral particles ( Cordier-Bussat et al, 1993 ; Baumforth et al, 1999 ). During lytic replication viral gene expression including glycoprotein 350/220, BZLF-1, BRLF1 promotes reactivation and triggers lytic replication through infected lymphocytes through the circulation to the central nervous system (CNS) ( Jha et al, 2015 ; Houen and Trier, 2020 ; Lupia et al, 2020 ).…”