Journal of NeuroVirologyPub Date : 2024-04-01Epub Date: 2024-03-12DOI: 10.1007/s13365-024-01195-x
Eran Frank Shorer, Leah H Rubin, Audrey L French, Kathleen M Weber, Elizabeth Daubert, Tsion Yohannes, Ralph Morack, Clary Clish, Kevin Bullock, Deborah Gustafson, Anjali Sharma, Andrea C Rogando, Qibin Qi, Helen J Burgess, Raha M Dastgheyb
{"title":"Tryptophan-kynurenine metabolic pathway and daytime dysfunction in women with HIV.","authors":"Eran Frank Shorer, Leah H Rubin, Audrey L French, Kathleen M Weber, Elizabeth Daubert, Tsion Yohannes, Ralph Morack, Clary Clish, Kevin Bullock, Deborah Gustafson, Anjali Sharma, Andrea C Rogando, Qibin Qi, Helen J Burgess, Raha M Dastgheyb","doi":"10.1007/s13365-024-01195-x","DOIUrl":"10.1007/s13365-024-01195-x","url":null,"abstract":"<p><p>Sleep disturbances are prevalent in women with HIV (WWH). Tryptophan-kynurenine (T-K) pathway metabolites are associated with alterations in actigraphy derived sleep measures in WWH, although may not always correlate with functional impairment. We investigated the relationship between T-K pathway metabolites and self-reported daytime dysfunction in WWH and women without HIV (WWoH). 141 WWH on stable antiretroviral therapy and 140 demographically similar WWoH enrolled in the IDOze Study had targeted plasma T-K metabolites measured using liquid chromatography-tandem mass spectrometry. We utilized the daytime dysfunction component of the Pittsburgh Sleep Quality Index (PSQI) to assess functional impairment across HIV-serostatus. Lower levels of 5-hydroxytryptophan and serotonin were associated with greater daytime dysfunction in all women. In WWH, daytime dysfunction was associated with increased kynurenic acid (R = 0.26, p < 0.05), and kynurenic acid-tryptophan (KA-T) ratio (R = 0.28, p < 0.01). WWH with daytime dysfunction had a 0.7 log fold increase in kynurenic acid compared to WWH without daytime dysfunction. Kynurenic acid levels and the KA-T ratio were associated with daytime dysfunction in WWH but not in WWoH. Longitudinal studies are needed to establish a causal relationship and directionality between T-K metabolic changes and sleep impairment in WWH.</p>","PeriodicalId":16665,"journal":{"name":"Journal of NeuroVirology","volume":" ","pages":"122-130"},"PeriodicalIF":1.9,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11531856/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140110445","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}
Journal of NeuroVirologyPub Date : 2024-04-01Epub Date: 2024-05-22DOI: 10.1007/s13365-024-01213-y
Nisrine El Moussaoui, Nicolas Lambert, Majdouline El Moussaoui, Elettra Bianchi, Philippe Léonard, Martin Moïse, Pierre Maquet
{"title":"Spinal cord involvement in progressive multifocal leukoencephalopathy and immune reconstitution inflammatory syndrome.","authors":"Nisrine El Moussaoui, Nicolas Lambert, Majdouline El Moussaoui, Elettra Bianchi, Philippe Léonard, Martin Moïse, Pierre Maquet","doi":"10.1007/s13365-024-01213-y","DOIUrl":"10.1007/s13365-024-01213-y","url":null,"abstract":"<p><p>Progressive multifocal leukoencephalopathy (PML) is an opportunistic infectious demyelinating disease of the central nervous system caused by JC polyomavirus predominantly affecting immunocompromised individuals. Nowadays, HIV, hematological malignancies and iatrogenic immune suppression account for most PML cases. For unknown reasons, spinal cord is classically protected from PML lesions. Here, we report the course of a patient harboring spinal cord lesions in the context of PML with immune reconstitution inflammatory syndrome and review the eight other cases reported in the literature so far. Then, we discuss the evolving spectrum of PML over recent years, potentially making its diagnosis more challenging.</p>","PeriodicalId":16665,"journal":{"name":"Journal of NeuroVirology","volume":" ","pages":"208-213"},"PeriodicalIF":2.3,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141081620","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":"Progressive multifocal leukoencephalopathy associated with systemic lupus erythematosus: longitudinal observation of lymphocytes, JC virus in cerebrospinal fluid, and brain magnetic resonance imaging","authors":"Hidetada Yamada, Megumi Toko, Masahiro Nakamori, Hiroki Ueno, Shiro Aoki, Tomohiro Sugimoto, Hiroko Yasutomi, Kazuo Nakamichi, Hirofumi Maruyama","doi":"10.1007/s13365-024-01203-0","DOIUrl":"https://doi.org/10.1007/s13365-024-01203-0","url":null,"abstract":"<p>Progressive multifocal leukoencephalopathy (PML) rarely occurs in patients with systemic lupus erythematosus (SLE). This report presents the case of a patient who developed PML due to SLE-associated multiple factors. A 60-year-old woman diagnosed with SLE undergoing multiple immunosuppressive therapies, including azathioprine, presented with cerebral cortical symptoms, lymphocytopenia, and vitamin B12 deficiency and was subsequently diagnosed with SLE-associated PML. We evaluated the cause and disease activity of PML, focusing on the longitudinal assessment of lymphocytopenia, JC virus (JCV) DNA copy number in the cerebrospinal fluid, and magnetic resonance imaging (MRI) findings. Discontinuing azathioprine and initiating alternative immunosuppressive treatments with intramuscular vitamin B12 injections affected lymphocytopenia and disease management. However, despite recovery from lymphopenia and JCV DNA copy number being low, the large hyperintense and punctate lesions observed on the fluid-attenuated inversion recovery (FLAIR) images exhibited varying behaviors, indicating that the balance between contributing factors for PML may have fluctuated after the initial treatment. Clinicians should be meticulous when assessing the underlying pathology of the multifactorial causes of PML due to SLE. The difference in the transition pattern of these lesions on FLAIR images may be one of the characteristics of MRI findings in PML associated with SLE, reflecting fluctuations in disease activity and the progression stage of PML.</p>","PeriodicalId":16665,"journal":{"name":"Journal of NeuroVirology","volume":"21 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140165631","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}
Joel A. Wood, Srilakshmi Chaparala, Cecilia Bantang, Ansuman Chattopadhyay, Maribeth A. Wesesky, Paul R. Kinchington, Vishwajit L. Nimgaonkar, David C. Bloom, Leonardo D’Aiuto
{"title":"RNA-Seq time-course analysis of neural precursor cell transcriptome in response to herpes simplex Virus-1 infection","authors":"Joel A. Wood, Srilakshmi Chaparala, Cecilia Bantang, Ansuman Chattopadhyay, Maribeth A. Wesesky, Paul R. Kinchington, Vishwajit L. Nimgaonkar, David C. Bloom, Leonardo D’Aiuto","doi":"10.1007/s13365-024-01198-8","DOIUrl":"https://doi.org/10.1007/s13365-024-01198-8","url":null,"abstract":"<p>The neurogenic niches within the central nervous system serve as essential reservoirs for neural precursor cells (NPCs), playing a crucial role in neurogenesis. However, these NPCs are particularly vulnerable to infection by the herpes simplex virus 1 (HSV-1). In the present study, we investigated the changes in the transcriptome of NPCs in response to HSV-1 infection using bulk RNA-Seq, compared to those of uninfected samples, at different time points post infection and in the presence or absence of antivirals. The results showed that NPCs upon HSV-1 infection undergo a significant dysregulation of genes playing a crucial role in aspects of neurogenesis, including genes affecting NPC proliferation, migration, and differentiation. Our analysis revealed that the CREB signaling, which plays a crucial role in the regulation of neurogenesis and memory consolidation, was the most consistantly downregulated pathway, even in the presence of antivirals. Additionally, cholesterol biosynthesis was significantly downregulated in HSV-1-infected NPCs. The findings from this study, for the first time, offer insights into the intricate molecular mechanisms that underlie the neurogenesis impairment associated with HSV-1 infection.</p>","PeriodicalId":16665,"journal":{"name":"Journal of NeuroVirology","volume":"19 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140116375","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":"Simian varicella virus infection and reactivation in rhesus macaques trigger cytokine and Aβ40/42 alterations in serum and cerebrospinal fluid","authors":"","doi":"10.1007/s13365-024-01196-w","DOIUrl":"https://doi.org/10.1007/s13365-024-01196-w","url":null,"abstract":"<h3>Abstract</h3> <p>Simian varicella virus (SVV) produces peripheral inflammatory responses during varicella (primary infection) and zoster (reactivation) in rhesus macaques (RM). However, it is unclear if peripheral measures are accurate proxies for central nervous system (CNS) responses. Thus, we analyzed cytokine and Aβ42/Aβ40 changes in paired serum and cerebrospinal fluid (CSF) during the course of infection. During varicella and zoster, every RM had variable changes in serum and CSF cytokine and Aβ42/Aβ40 levels compared to pre-inoculation levels. Overall, peripheral infection appears to affect CNS cytokine and Aβ42/Aβ40 levels independent of serum responses, suggesting that peripheral disease may contribute to CNS disease.</p>","PeriodicalId":16665,"journal":{"name":"Journal of NeuroVirology","volume":"84 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140056025","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}
Journal of NeuroVirologyPub Date : 2024-02-01Epub Date: 2024-01-27DOI: 10.1007/s13365-023-01186-4
Kara M Rademeyer, Sara R Nass, Austin M Jones, Michael Ohene-Nyako, Kurt F Hauser, MaryPeace McRae
{"title":"Fentanyl dysregulates neuroinflammation and disrupts blood-brain barrier integrity in HIV-1 Tat transgenic mice.","authors":"Kara M Rademeyer, Sara R Nass, Austin M Jones, Michael Ohene-Nyako, Kurt F Hauser, MaryPeace McRae","doi":"10.1007/s13365-023-01186-4","DOIUrl":"10.1007/s13365-023-01186-4","url":null,"abstract":"<p><p>Opioid overdose deaths have dramatically increased by 781% from 1999 to 2021. In the setting of HIV, opioid drug abuse exacerbates neurotoxic effects of HIV in the brain, as opioids enhance viral replication, promote neuronal dysfunction and injury, and dysregulate an already compromised inflammatory response. Despite the rise in fentanyl abuse and the close association between opioid abuse and HIV infection, the interactive comorbidity between fentanyl abuse and HIV has yet to be examined in vivo. The HIV-1 Tat-transgenic mouse model was used to understand the interactive effects between fentanyl and HIV. Tat is an essential protein produced during HIV that drives the transcription of new virions and exerts neurotoxic effects within the brain. The Tat-transgenic mouse model uses a glial fibrillary acidic protein (GFAP)-driven tetracycline promoter which limits Tat production to the brain and this model is well used for examining mechanisms related to neuroHIV. After 7 days of fentanyl exposure, brains were harvested. Tight junction proteins, the vascular cell adhesion molecule, and platelet-derived growth factor receptor-β were measured to examine the integrity of the blood brain barrier. The immune response was assessed using a mouse-specific multiplex chemokine assay. For the first time in vivo, we demonstrate that fentanyl by itself can severely disrupt the blood-brain barrier and dysregulate the immune response. In addition, we reveal associations between inflammatory markers and tight junction proteins at the blood-brain barrier.</p>","PeriodicalId":16665,"journal":{"name":"Journal of NeuroVirology","volume":" ","pages":"1-21"},"PeriodicalIF":2.3,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11232468/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139569767","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":"Meta-analysis of the serum/plasma proteome identifies significant associations between COVID-19 with Alzheimer's/Parkinson's diseases.","authors":"Althaf Mahin, Sreelakshmi Pathappillil Soman, Prashant Kumar Modi, Rajesh Raju, Thottethodi Subrahmanya Keshava Prasad, Chandran S Abhinand","doi":"10.1007/s13365-023-01191-7","DOIUrl":"10.1007/s13365-023-01191-7","url":null,"abstract":"<p><p>In recent years, we have seen the widespread devastations and serious health complications manifested by COVID-19 globally. Although we have effectively controlled the pandemic, uncertainties persist regarding its potential long-term effects, including prolonged neurological issues. To gain comprehensive insights, we conducted a meta-analysis of mass spectrometry-based proteomics data retrieved from different studies with a total of 538 COVID-19 patients and 523 healthy controls. The meta-analysis revealed that top-enriched pathways were associated with neurological disorders, including Alzheimer's (AD) and Parkinson's disease (PD). Further analysis confirmed a direct correlation in the expression patterns of 24 proteins involved in Alzheimer's and 23 proteins in Parkinson's disease with COVID-19. Protein-protein interaction network and cluster analysis identified SNCA as a hub protein, a known biomarker for Parkinson's disease, in both AD and PD. To the best of our knowledge, this is the first meta-analysis study providing proteomic profiling evidence linking COVID-19 to neurological complications.</p>","PeriodicalId":16665,"journal":{"name":"Journal of NeuroVirology","volume":" ","pages":"57-70"},"PeriodicalIF":3.2,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139087299","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}
Journal of NeuroVirologyPub Date : 2024-02-01Epub Date: 2024-01-03DOI: 10.1007/s13365-023-01187-3
Jasmina M Luczo, Sarah J Edwards, Katie Ardipradja, Willy W Suen, Gough G Au, Glenn A Marsh, Nathan Godde, Christina L Rootes, John Bingham, Vinod Sundaramoorthy
{"title":"SARS-CoV and SARS-CoV-2 display limited neuronal infection and lack the ability to transmit within synaptically connected axons in stem cell-derived human neurons.","authors":"Jasmina M Luczo, Sarah J Edwards, Katie Ardipradja, Willy W Suen, Gough G Au, Glenn A Marsh, Nathan Godde, Christina L Rootes, John Bingham, Vinod Sundaramoorthy","doi":"10.1007/s13365-023-01187-3","DOIUrl":"10.1007/s13365-023-01187-3","url":null,"abstract":"<p><p>Sarbecoviruses such as SARS and SARS-CoV-2 have been responsible for two major outbreaks in humans, the latter resulting in a global pandemic. While sarbecoviruses primarily cause an acute respiratory infection, they have been shown to infect the nervous system. However, mechanisms of sarbecovirus neuroinvasion and neuropathogenesis remain unclear. In this study, we examined the infectivity and trans-synaptic transmission potential of the sarbecoviruses SARS and SARS-CoV-2 in human stem cell-derived neural model systems. We demonstrated limited ability of sarbecoviruses to infect and replicate in human stem cell-derived neurons. Furthermore, we demonstrated an inability of sarbecoviruses to transmit between synaptically connected human stem cell-derived neurons. Finally, we determined an absence of SARS-CoV-2 infection in olfactory neurons in experimentally infected ferrets. Collectively, this study indicates that sarbecoviruses exhibit low potential to infect human stem cell-derived neurons, lack an ability to infect ferret olfactory neurons, and lack an inbuilt molecular mechanism to utilise retrograde axonal trafficking and trans-synaptic transmission to spread within the human nervous system.</p>","PeriodicalId":16665,"journal":{"name":"Journal of NeuroVirology","volume":" ","pages":"39-51"},"PeriodicalIF":3.2,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11035468/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139087300","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}
Jacqueline Renee Kulbe, Alexandra Anh Le, Michael Mante, Jazmin Florio, Anna Elizabeth Laird, Mary K Swinton, Robert A Rissman, Jerel Adam Fields
{"title":"Correction: GP120 and tenofovir alafenamide alter cannabinoid receptor 1 expression in hippocampus of mice.","authors":"Jacqueline Renee Kulbe, Alexandra Anh Le, Michael Mante, Jazmin Florio, Anna Elizabeth Laird, Mary K Swinton, Robert A Rissman, Jerel Adam Fields","doi":"10.1007/s13365-023-01192-6","DOIUrl":"10.1007/s13365-023-01192-6","url":null,"abstract":"","PeriodicalId":16665,"journal":{"name":"Journal of NeuroVirology","volume":" ","pages":"101-102"},"PeriodicalIF":3.2,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11035418/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139099477","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}
Journal of NeuroVirologyPub Date : 2024-02-01Epub Date: 2024-01-08DOI: 10.1007/s13365-023-01190-8
Annu Rani, Süleyman Ergün, Srikanth Karnati, Hem Chandra Jha
{"title":"Understanding the link between neurotropic viruses, BBB permeability, and MS pathogenesis.","authors":"Annu Rani, Süleyman Ergün, Srikanth Karnati, Hem Chandra Jha","doi":"10.1007/s13365-023-01190-8","DOIUrl":"10.1007/s13365-023-01190-8","url":null,"abstract":"<p><p>Neurotropic viruses can infiltrate the CNS by crossing the blood-brain barrier (BBB) through various mechanisms including paracellular, transcellular, and \"Trojan horse\" mechanisms during leukocyte diapedesis. These viruses belong to several families, including retroviruses; human immunodeficiency virus type 1 (HIV-1), flaviviruses; Japanese encephalitis (JEV); and herpesviruses; herpes simplex virus type 1 (HSV-1), Epstein-Barr virus (EBV), and mouse adenovirus 1 (MAV-1). For entering the brain, viral proteins act upon the tight junctions (TJs) between the brain microvascular endothelial cells (BMECs). For instance, HIV-1 proteins, such as glycoprotein 120, Nef, Vpr, and Tat, disrupt the BBB and generate a neurotoxic effect. Recombinant-Tat triggers amendments in the BBB by decreasing expression of the TJ proteins such as claudin-1, claudin-5, and zona occludens-1 (ZO-1). Thus, the breaching of BBB has been reported in myriad of neurological diseases including multiple sclerosis (MS). Neurotropic viruses also exhibit molecular mimicry with several myelin sheath proteins, i.e., antibodies against EBV nuclear antigen 1 (EBNA1) aa411-426 cross-react with MBP and EBNA1 aa385-420 was found to be associated with MS risk haplotype HLA-DRB1*150. Notably, myelin protein epitopes (PLP<sub>139-151</sub>, MOG<sub>35-55</sub>, and MBP<sub>87-99</sub>) are being used to generate model systems for MS such as experimental autoimmune encephalomyelitis (EAE) to understand the disease mechanism and therapeutics. Viruses like Theiler's murine encephalomyelitis virus (TMEV) are also commonly used to generate EAE. Altogether, this review provide insights into the viruses' association with BBB leakiness and MS along with possible mechanistic details which could potentially use for therapeutics.</p>","PeriodicalId":16665,"journal":{"name":"Journal of NeuroVirology","volume":" ","pages":"22-38"},"PeriodicalIF":3.2,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139377866","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}