Journal of NeuroVirology最新文献

{"title":"Upregulation of microRNAs correlates with downregulation of HERV-K expression in Parkinson's disease.","authors":"Elena Rita Simula, Somaye Jasemi, Kay Paulus, Leonardo Antonio Sechi","doi":"10.1007/s13365-024-01234-7","DOIUrl":"https://doi.org/10.1007/s13365-024-01234-7","url":null,"abstract":"<p><p>Human endogenous retroviruses (HERVs) involvement in neurological diseases has been extensively documented, although the etiology of HERV reactivation remains unclear. MicroRNAs represent one of the potential regulatory mechanisms of HERV reactivation. We identified fourteen microRNAs predicted to bind the HERV-K transcript, and subsequently analyzed for their gene expression levels alongside those of HERV-K. We documented an increased expression of four microRNAs in patients with Parkinson's disease compared to healthy controls, which correlated with a downregulation of HERV-K transcripts. We hypothesize that specific microRNAs may bind to HERV-K transcripts, leading to its downregulation.</p>","PeriodicalId":16665,"journal":{"name":"Journal of NeuroVirology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Greater humoral EBV response may be associated with choroid plexus inflammation in progressive MS.","authors":"Dejan Jakimovski, Robert Zivadinov, Murali Ramanathan, Bianca Weinstock-Guttman, Eleonora Tavazzi, Michael G Dwyer, Niels Bergsland","doi":"10.1007/s13365-024-01231-w","DOIUrl":"https://doi.org/10.1007/s13365-024-01231-w","url":null,"abstract":"<p><p>Choroid plexus (CP) inflammation can be quantified in vivo with MRI in people with multiple sclerosis (pwMS). It remains unknown whether Epstein Barr Virus (EBV) is related to CP changes. Total of 170 pwMS (116 relapsing-remitting; RRMS and 54 progressive MS; PMS) underwent MRI examination and measurement of humoral anti-EBV response. CP volume and CP pseudo-T2 (pT2), a relaxation time indicative of edema and neuroinflammation, were measured. Moreover, anti-EBV nuclear antigen-1 (EBNA-1) IgG and anti-EBV capsid antigen (VCA) IgG antibodies were measured. The PMS group had greater CP pT2 value when compared to RRMS (1120ms vs. 954ms, p = 0.037). After adjusting for age and therapy effects, higher CP pT2 values were associated with higher anti-EBNA-1 IgG levels only in PMS (r = 0.352, p = 0.015). Higher Anti-EBV humoral response in pwMS may be associated with increased CP neuroinflammatory changes and may be more relevant for the later chronic stage of the disease. Large-scale studies should investigate whether these findings are generalizable to all types of progressive MS.</p>","PeriodicalId":16665,"journal":{"name":"Journal of NeuroVirology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation of voltage-gated sodium channels by TNF-α during herpes simplex virus latency establishment.","authors":"Qiaojuan Zhang, Shao-Chung Hsia, Miguel Martin-Caraballo","doi":"10.1007/s13365-024-01229-4","DOIUrl":"10.1007/s13365-024-01229-4","url":null,"abstract":"<p><p>During lytic or latent infection of sensory neurons with herpes simplex virus type 1 (HSV-1) there are significant changes in the expression of voltage-gated Na⁺ channels, which may disrupt the transmission of pain information. HSV-1 infection can also evoke the secretion of various pro-inflammatory cytokines, including TNF-α and IL-6. In this work, we hypothesized that TNF-α regulates the expression of Na⁺ channels during HSV-1 latency establishment in ND7/23 sensory-like neurons. Latency establishment was mimicked by culturing HSV-1 infected ND7/23 cells in the presence of acyclovir (ACV) for 3 days. Changes in the functional expression of voltage-gated Na⁺ channels were assessed by whole-cell recordings. Our results demonstrate that infection of ND7/23 cells with the HSV-1 strain McKrae with GFP expression (M-GFP) causes a significant decrease in sodium currents during latency establishment. Exposure of ND7/23 cells to TNF-α during latency establishment reverses the effect of HSV-1, resulting in a significant increase in sodium current density. However, Na⁺ currents were not restored by 3 day-treatment with IL-6. There were no changes in the pharmacological and biophysical properties of sodium currents promoted by TNF-α, including sensitivity to tetrodotoxin and the current-voltage relationship. TNF-α stimulation of ND7/23 cells increases p38 signaling. Inhibition of p38 signaling with SB203580 or SB202190 eliminates the stimulatory effect of TNF-α on sodium currents. These results indicate that TNF-α signaling in sensory neurons during latency establishment upregulates the expression of voltage-gated Na⁺ channels in order to maintain the transmission of pain information.</p>","PeriodicalId":16665,"journal":{"name":"Journal of NeuroVirology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Substance use moderates relationships between apolipoprotein E genotype, hepatitis C, cognition, and depression in Miami Adult Studies on HIV (MASH) participants.","authors":"Shanna L Burke, Adrienne Grudzien, Tan Li, Stephanie Garcia, Sabrina Sales Martinez, Emily Jurich, Daniel R Jimenez, Jacqueline Hernández, Qingyun Liu, Tahirah A Tyrell, Adriana L Campa, Anglique Johnson, Zoran Bursac, Marianna K Baum","doi":"10.1007/s13365-024-01225-8","DOIUrl":"10.1007/s13365-024-01225-8","url":null,"abstract":"<p><p>The impact of APOE on HIV and HCV disease course, cognition, and memory has been understudied in minoritized populations. This study examined whether scores on cognition and depression measures differed by APOE ε4 carrier status while considering HCV and HIV seropositivity and whether these measures were moderated by substance use. A retrospective analysis examined cognitive and psychological data from participants (n = 493) in the Miami Adult Studies on HIV (MASH) cohort. APOE genotyping was performed on banked blood samples. Multiple linear regression was employed to examine differences across participants living with and without HIV and/or HCV and by APOE ε4 genotype. APOE ε4 carriers living with HCV who used cannabis had higher depression scores than non-ε4 carriers, while nonusers had fewer depressive symptoms. APOE ε4 carriers living with HCV had better cognition scores after adjusting for cocaine, opiate, and cannabis use than non-ε4 carriers. Scores on cognitive and depression measures did not differ between APOE ε4 carriers and non-ε4 carriers in participants living with HIV, and substance use did not moderate this relationship. This study was the first of its kind to examine substance use as a moderator for cognition and depression among individuals with HIV and/or HCV stratified by APOE genotype. Findings support further research evaluating the frequency and duration of 1) domains of cognitive functioning impacted by APOE genotype relevant to substance use and 2) the influence of substance use on cognitive and depressive outcomes among adults living with HIV and HCV, HIV, or HCV.</p>","PeriodicalId":16665,"journal":{"name":"Journal of NeuroVirology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141971319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CD4 nadir and neurocognitive trajectories in people living with HIV.","authors":"Razmig Garabet, Will Dampier, Shinika Tillman, Kim Malone, Zsofia Szep, Amy Althoff, Vanessa Pirrone, Michael R Nonnemacher, Brian Wigdahl, Maria Schultheis, Kathryn N Devlin","doi":"10.1007/s13365-024-01217-8","DOIUrl":"10.1007/s13365-024-01217-8","url":null,"abstract":"<p><p>Human immunodeficiency virus-associated neurocognitive disorders persist in the combination antiretroviral therapy era. CD4 nadir is a well-established predictor of cognition cross-sectionally, but its impact on longitudinal neurocognitive (NC) trajectories is unclear. The few studies on this topic examined trajectories of global cognition, rather than specific NC domains. The current study examined CD4 nadir in relation to domain-specific NC decline. 132 HIV + adults from the Temple/Drexel Comprehensive NeuroHIV Center, Clinical and Translational Research Support Core Cohort were administered comprehensive NC assessments longitudinally, with last visit occurring an average of 12 years after CD4 nadir. Linear mixed models were used to examine CD4 nadir in relation to longitudinal NC trajectories in three empirically identified NC domains: speed/executive function (S/EF), visuospatial memory (VM), and verbal fluency (VF). CD4 nadir was associated with change in VF (p = 0.020), but not with S/EF or VM. Specifically, those with CD4 nadir < 200 demonstrated increasing VF over time (p = .002), whereas those with CD4 nadir > 200 demonstrated stable VF (p = .568), though these differing trajectories may partly reflect regression to the mean or differential practice effect. CD4 dynamics over time were analyzed as potential mechanisms for the identified associations, with mixed findings. While low CD4 nadir has been associated with weaker neurocognition among people living with HIV, the results of this study suggest that low CD4 nadir is not associated with ongoing decline a decade later. Nadir-related deficits in VF may be stable or even improve over time, possibly reflecting the beneficial cognitive effects of long-term treatment and immune reconstitution.</p>","PeriodicalId":16665,"journal":{"name":"Journal of NeuroVirology","volume":" ","pages":"423-433"},"PeriodicalIF":2.3,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11512832/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141296223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of HIV variants from paired Cerebrospinal fluid and Plasma samples in primary microglia and CD4⁺ T-cells.","authors":"Stephanie B H Gumbs, Arjen J Stam, Tania Mudrikova, Pauline J Schipper, Andy I M Hoepelman, Petra M van Ham, Anne L Borst, LMarije Hofstra, Lavina Gharu, Stephanie van Wyk, Eduan Wilkinson, Lot D de Witte, Annemarie M J Wensing, Monique Nijhuis","doi":"10.1007/s13365-024-01207-w","DOIUrl":"10.1007/s13365-024-01207-w","url":null,"abstract":"<p><p>Despite antiretroviral therapy (ART), HIV persistence in the central nervous system (CNS) continues to cause a range of cognitive impairments in people living with HIV (PLWH). Upon disease progression, transmigrating CCR5-using T-cell tropic viruses are hypothesized to evolve into macrophage-tropic viruses in the CNS that can efficiently infect low CD4-expressing cells, such as microglia. We examined HIV-1 RNA concentration, co-receptor usage, and CSF compartmentalization in paired CSF and blood samples from 19 adults not on treatment. Full-length envelope CSF- and plasma-derived reporter viruses were generated from 3 subjects and phenotypically characterized in human primary CD4⁺ T-cells and primary microglia. Median HIV RNA levels were higher in plasma than in CSF (5.01 vs. 4.12 log10 cp/mL; p = 0.004), and coreceptor usage was mostly concordant for CCR5 across the paired samples (n = 17). Genetically compartmentalized CSF viral populations were detected in 2 subjects, one with and one without neurological symptoms. All viral clones could replicate in T-cells (R5 T cell-tropic). In addition, 3 CSF and 1 plasma patient-derived viral clones also had the capacity to replicate in microglia/macrophages and, therefore have an intermediate macrophage tropic phenotype. Overall, with this study, we demonstrate that in a subset of PLWH, plasma-derived viruses undergo genetic and phenotypic evolution within the CNS, indicating viral infection and replication in CNS cells. It remains to be studied whether the intermediate macrophage-tropic phenotype observed in primary microglia represents a midpoint in the evolution towards a macrophage-tropic phenotype that can efficiently replicate in microglial cells and propagate viral infection in the CNS.</p>","PeriodicalId":16665,"journal":{"name":"Journal of NeuroVirology","volume":" ","pages":"380-392"},"PeriodicalIF":2.3,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11512886/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140863414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Suppression of HIV-TAT and cocaine-induced neurotoxicity and inflammation by cell penetrable itaconate esters.","authors":"B Celia Cui, Marina Aksenova, Aliaksandra Sikirzhytskaya, Diana Odhiambo, Elizaveta Korunova, Vitali Sikirzhytski, Hao Ji, Diego Altomare, Eugenia Broude, Norma Frizzell, Rosemarie Booze, Michael D Wyatt, Michael Shtutman","doi":"10.1007/s13365-024-01216-9","DOIUrl":"10.1007/s13365-024-01216-9","url":null,"abstract":"<p><p>HIV-associated neurological disorder (HAND) is a serious complication of HIV infection marked by neurotoxicity induced by viral proteins like Tat. Substance abuse exacerbates neurocognitive impairment in people living with HIV. There is an urgent need for therapeutic strategies to combat HAND comorbid with Cocaine Use Disorder (CUD). Our analysis of HIV and cocaine-induced transcriptomes in primary cortical cultures revealed significant overexpression of the macrophage-specific gene aconitate decarboxylase 1 (Acod1). The ACOD1 protein converts the tricarboxylic acid intermediate cis-aconitate into itaconate during the activation of inflammation. Itaconate then facilitates cytokine production and activates anti-inflammatory transcription factors, shielding macrophages from infection-induced cell death. However, the immunometabolic function of itaconate was unexplored in HIV and cocaine-exposed microglia. We assessed the potential of 4-octyl-itaconate (4OI), a cell-penetrable ester form of itaconate known for its anti-inflammatory properties. When primary cortical cultures exposed to Tat and cocaine were treated with 4OI, microglial cell number increased and the morphological altercations induced by Tat and cocaine were reversed. Microglial cells also appeared more ramified, resembling the quiescent microglia. 4OI treatment inhibited secretion of the proinflammatory cytokines IL-1α, IL-1β, IL-6, and MIP1-α induced by Tat and cocaine. Transcriptome profiling determined that Nrf2 target genes were significantly activated in Tat and 4OI treated cultures relative to Tat alone. Further, genes associated with cytoskeleton dynamics in inflammatory microglia were downregulated by 4OI treatment. Together, the results strongly suggest 4-octyl-itaconate holds promise as a potential candidate for therapeutic development to treat HAND coupled with CUD comorbidities.</p>","PeriodicalId":16665,"journal":{"name":"Journal of NeuroVirology","volume":" ","pages":"337-352"},"PeriodicalIF":2.3,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11512888/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141331137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Progressive multifocal leukoencephalopathy in sarcoidosis successfully treated with pembrolizumab.","authors":"Gizem Öztürk, Elif İrem Tekeli, Seyda Erdoğan, Elif Peker, Canan Yücesan","doi":"10.1007/s13365-024-01227-6","DOIUrl":"10.1007/s13365-024-01227-6","url":null,"abstract":"<p><p>Progressive multifocal leukoencephalopathy (PML) is a severe, demyelinating disease of the central nervous system caused by JC virus infection. The disease can be seen in sarcoidosis patients without additional risk factors. Here, we present an individual with PML secondary to sarcoidosis treated with 8 doses of pembrolizumab, a Programmed Cell-Death-1 (PD-1) Immune Checkpoint Inhibitor who showed significant improvement. This report illustrates the objective clinical and radiological improvement in a patient with PML due to sarcoidosis, and suggests further study of immune checkpoint inhibitors as a potential treatment for sarcoidosis patients with PML.</p>","PeriodicalId":16665,"journal":{"name":"Journal of NeuroVirology","volume":" ","pages":"441-444"},"PeriodicalIF":2.3,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142000189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Type 2 herpes simplex virus-induced anti-N-methyl-D-aspartate receptor encephalitis responsive to immunoglobulin monotherapy.","authors":"Er-Chuang Li, Qi-Lun Lai, Tian-Yi Zhang, Bing-Qing Du, Jing Zhao, Meng-Ting Cai, Yin-Xi Zhang, Gao-Li Fang","doi":"10.1007/s13365-024-01228-5","DOIUrl":"10.1007/s13365-024-01228-5","url":null,"abstract":"<p><p>Herpes simplex virus-2 encephalitis (HSV2E) in immunocompetent adults is exceptionally rare, and the subsequent onset of autoimmune encephalitis after HSV2E is even less common. This report presents the inaugural Chinese case of anti-N-methyl-D-aspartate receptor encephalitis (NMDARE) induced by HSV2E, confirmed via metagenomic next-generation sequencing (mNGS). The patient demonstrated a favorable response to intravenous immunoglobulin (IVIG) monotherapy. This case emphasizes the importance of considering autoimmune encephalitis in patients exhibiting new or recurrent neurological symptoms after HSV2E recovery. Comprehensive mNGS and neuronal antibody testing are essential for timely diagnosis. Moreover, IVIG monotherapy can serve as an effective treatment for NMDARE induced by HSV2, providing a viable alternative, particularly when steroid therapy is contraindicated.</p>","PeriodicalId":16665,"journal":{"name":"Journal of NeuroVirology","volume":" ","pages":"445-449"},"PeriodicalIF":2.3,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142000190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human endogenous retrovirus W in multiple sclerosis: transcriptional activity is associated with decline in oligodendrocyte proportions in the white matter of the brain.","authors":"Tapio Nevalainen, Arttu Autio-Kimura, Mikko Hurme","doi":"10.1007/s13365-024-01208-9","DOIUrl":"10.1007/s13365-024-01208-9","url":null,"abstract":"<p><p>Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease. One of the basic mechanisms in this disease is the autoimmune response against the myelin sheet leading to axonal damage. There is strong evidence showing that this response is regulated by both genetic and environmental factors. In addition, the role of viruses has been extensively studied, especially in the case of human endogenous retroviruses (HERVs). However, although several associations with MS susceptibility, especially in the case of HERV-W family have been observed, the pathogenic mechanisms have remained enigmatic. To clarify these HERV-mediated mechanisms as well as the responsible HERV-W loci, we utilized RNA sequencing data obtained from the white matter of the brain of individuals with and without MS. CIBERSORTx tool was applied to estimate the proportions of neuronal, glial, and endothelial cells in the brain. In addition, the transcriptional activity of 215 HERV-W loci were analyzed. The results indicated that 65 HERV-W loci had detectable expression, of which 14 were differentially expressed between MS and control samples. Of these, 12 HERV-W loci were upregulated in MS. Expression levels of the 8 upregulated HERV-W loci had significant negative correlation with estimated oligodendrocyte proportions, suggesting that they are associated with the dynamics of oligodendrocyte generation and/or maintenance. Furthermore, Gene Set Enrichment Analysis (GSEA) results indicated that expression levels of three upregulated HERV-W loci: 2p16.2, 2q13, and Xq13.3, are associated with suppression of oligodendrocyte development and myelination. Taken together, these data suggest new HERV-W loci candidates that might take part in MS pathogenesis.</p>","PeriodicalId":16665,"journal":{"name":"Journal of NeuroVirology","volume":" ","pages":"393-405"},"PeriodicalIF":2.3,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11512866/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140876698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}