Journal of NeuroVirology最新文献

{"title":"Correction: Performance of the national institute of infectious diseases disability scale in HTLV-1-associated myelopathy/tropical spastic paraparesis.","authors":"Felipe R Schmidt, Evandro S F Coutinho, Marco A Lima, Marcus T T Silva, Ana C C B Leite, Igor O Fonseca, Abelardo Q C Araujo","doi":"10.1007/s13365-023-01188-2","DOIUrl":"10.1007/s13365-023-01188-2","url":null,"abstract":"","PeriodicalId":16665,"journal":{"name":"Journal of NeuroVirology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138460502","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":"HSV-1 latency-associated transcript miR-H3 and miR-H4 target STXBP1 and GABBR2 genes.","authors":"Karrar Mahmood Shaker Al-Khfaji, Nika Kooshki Zamani, Ehsan Arefian","doi":"10.1007/s13365-023-01174-8","DOIUrl":"10.1007/s13365-023-01174-8","url":null,"abstract":"<p><p>During latent infection, the HSV-1 virus generates only a single transcript, LAT, which encodes six miRNAs. The GABAergic pathway signaling system is an essential cell signaling pathway influenced by various therapeutic targets and some brain disorders, such as epilepsy. This study found that miRNAs encoding LAT might target the STXBP1 and GABBR2 genes, which are among the significant genes in the GABAergic pathway. Bioinformatic analysis utilizing TargetScan version 5.2 and the RNA22 tools uncovered miRNAs encoding LAT that can influence STXBP1 and GABBR2 transcripts. To evaluate the targeting effect of candidate microRNAs encoding LAT, namely, miR-H3 and miR-H4, LAT constructs were transfected into HEK 293T cells. The expression levels of microRNAs encoding LAT, as well as STXBP1 and GABBR2, were assayed by real-time PCR. Finally, the targeting potential of STXBP1 and GABBR2 3'UTR by LAT-encoded microRNAs was evaluated by the luciferase assay. In the current study, the bioinformatic tool TargetScan demonstrated that miR-H3 has the potential to target the transcripts of the STXBP1 and GABBR2 genes, whereas miR-H4 solely targeted GABBR2. On the other hand, the bioinformatic tool RNA22 validated the potential targeting of STXBP1 and GABBR2 by miR-H3 and miR-H4. Our findings showed that overexpression of miR-H4, miR-H3, or LAT significantly decreased STXBP1 gene expression by an average of 0.0593-fold, 0.237-fold, and 0.84-fold, respectively. Similarly, overexpression of miR-H3 or miR-H4 decreased GABBR2 expression by an average of 0.055- or 0.687-fold, respectively. Notably, targeting the GABBR2 3'UTR with the LAT transcript had no detectable effect. The evaluation of the targeting potential of STXBP1 and GABBR2 3'UTR by microRNAs encoded by LAT was conducted with a luciferase assay. Our results showed that miR-H3 overexpression reduces Renilla expression in psiCHECK2 plasmids with STXBP1 or GABBR2 3'UTR genes by 0.62- and 0.55-fold, respectively. miR-H4 reduced Renilla gene expression regulated by GABBR2's 3'UTR plasmid but had no effect on the Renilla gene expression regulated by STXBP1's 3'UTR. When the LAT transcript was overexpressed, there was a decrease in Renilla expression by 0.44-fold because of the regulation of STXBP1's 3'UTR. However, there was no significant effect observed through the control of GABBR2's 3'UTR.</p>","PeriodicalId":16665,"journal":{"name":"Journal of NeuroVirology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10154500","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":"Pembrolizumab for the treatment of progressive multifocal leukoencephalopathy in China.","authors":"Siyuan Fan, Mange Liu, Lin Bai, Sixian Chen, Bo Hou, Nan Lin, Jing Yuan, Chenhui Mao, Jingwen Niu, Haitao Ren, Yanhuan Zhao, Zaiqiang Zhang, Yicheng Zhu, Bin Peng, Hongzhi Guan","doi":"10.1007/s13365-023-01180-w","DOIUrl":"10.1007/s13365-023-01180-w","url":null,"abstract":"<p><p>The aim of this study is to analyze the clinical characteristics and outcomes of Chinese patients with progressive multifocal leukoencephalopathy (PML) who were treated with programmed cell death protein 1 (PD1) blockade therapies. We retrospectively analyzed patients who were admitted to our hospital between October 1, 2020, and October 1, 2022, diagnosed with PML and treated with PD1 blockade therapies. Four patients with PML who were treated with PD1 blockade therapies were identified. All patients were male, and their ages ranged from 19 to 54 years old. One patient (Case 2) exhibited mild pleocytosis, while three patients (Cases 2-4) had markedly reduced T lymphocyte cell counts prior to treatment. The time interval between symptom onset and treatment initiation ranged from six to 54 weeks. All patients received pembrolizumab treatment, with a total of two to four doses administered. Three patients who responded to pembrolizumab treatment showed clinical improvement starting around 8 weeks after the initiation of therapy. Although one patient did not show clinical improvement, they ultimately survived until the last follow-up. None of the patients in this study exhibited immune-related adverse events or immune reconstitution inflammatory syndrome. PD1 blockade appears to be a promising novel therapeutic option for PML; additional prospective studies are necessary to confirm its efficacy.</p>","PeriodicalId":16665,"journal":{"name":"Journal of NeuroVirology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66784001","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":"Acute cerebellitis following COVID-19 infection associated with autoantibodies to glutamate receptors: a case report.","authors":"Takuya Watanabe, Yuki Kakinuma, Keiko Watanabe, Ryuta Kinno","doi":"10.1007/s13365-023-01183-7","DOIUrl":"10.1007/s13365-023-01183-7","url":null,"abstract":"<p><p>While COVID-19 infection by the SARS-CoV-2 virus was initially identified as a respiratory disease, mounting evidence suggests its association with various neurological issues as well. Notably, COVID-19 has been linked to acute cerebellitis (AC) and post-infectious cerebellar ataxia. The precise underlying mechanisms behind these neurological effects remain unclear. Our case report describes AC following COVID-19 infection, associated with autoantibodies to glutamate receptors (GluRs), hinting at immunological involvement. The case is a 56-year-old woman who experienced fever and fatigue due to COVID-19 infection. About 2 weeks after these symptoms improved, she showed cerebellar symptoms such as ocular overshoot and ataxia when presenting to our hospital. Her cerebrospinal fluid (CSF) findings were normal. Brain MRI revealed cerebellar abnormalities. Treatment with methylprednisolone led to symptom improvement. Later tests of CSF yielded positive results for autoantibodies to GluRs. Our findings suggest a possible immune-mediated mechanism in the onset of AC following COVID-19 infection. Clinicians should consider the possibility of immunological pathogenesis when diagnosing cerebellar symptoms after COVID-19 infection.</p>","PeriodicalId":16665,"journal":{"name":"Journal of NeuroVirology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10794470/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71482727","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":"Application of VirCapSeq-VERT and BacCapSeq in the diagnosis of presumed and definitive neuroinfectious diseases.","authors":"Abhilasha P Boruah, Adam Kroopnick, Riddhi Thakkar, Anne E Wapniarski, Carla Kim, Rachelle Dugue, Eileen Harrigan, W Ian Lipkin, Nischay Mishra, Kiran T Thakur","doi":"10.1007/s13365-023-01172-w","DOIUrl":"10.1007/s13365-023-01172-w","url":null,"abstract":"<p><p>Unbiased high-throughput sequencing (HTS) has enabled new insights into the diversity of agents implicated in central nervous system (CNS) infections. The addition of positive selection capture methods to HTS has enhanced the sensitivity while reducing sequencing costs and the complexity of bioinformatic analysis. Here we report the use of virus capture-based sequencing for vertebrate viruses (VirCapSeq-VERT) and bacterial capture sequencing (BacCapSeq) in investigating CNS infections. Thirty-four samples were categorized: (1) patients with definitive CNS infection by routine testing; (2) patients meeting clinically the Brighton criteria (BC) for meningoencephalitis; (3) patients with presumptive infectious etiology highest on the differential. RNA extracts from cerebrospinal fluid (CSF) were used for VirCapSeq-VERT, and DNA extracts were used for BacCapSeq analysis. Among 8 samples from known CNS infections in group 1, VirCapSeq and BacCapSeq confirmed 3 expected diagnoses (42.8%), were negative in 2 (25%), yielded an alternative result in 1 (11.1%), and did not detect 2 expected negative pathogens. The confirmed cases identified HHV-6, HSV-2, and VZV while the negative samples included JCV and HSV-2. In groups 2 and 3, 11/26 samples (42%) were positive for at least one pathogen; however, 27% of the total samples (7/26) were positive for commensal organisms. No microbial nucleic acids were detected in negative control samples. HTS showed limited promise for pathogen identification in presumed CNS infectious diseases in our small sample. Before conducting larger-scale prospective studies to assess the clinical value of this novel technique, clinicians should understand the benefits and limitations of using this modality.</p>","PeriodicalId":16665,"journal":{"name":"Journal of NeuroVirology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41236194","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":"Characterizing Epstein-Barr virus infection of the central nervous system in Zambian adults living with HIV.","authors":"Kalo Musukuma-Chifulo, Musie Ghebremichael, Obvious Nchimunya Chilyabanyama, Matthew Bates, Sody Munsaka, Michelo Simuyandi, Caroline Chisenga, John Tembo, Edford Sinkala, Igor J Koralnik, Xin Dang, Roma Chilengi, Omar K Siddiqi","doi":"10.1007/s13365-023-01178-4","DOIUrl":"10.1007/s13365-023-01178-4","url":null,"abstract":"<p><p>The significance of Epstein-Barr virus (EBV) detection in the cerebrospinal spinal fluid (CSF) in people living with HIV (PLWH) is not entirely understood. The detection of EBV DNA may represent active central nervous system (CNS) infection, reactivation in the setting of another CNS pathogen or due to impaired immunity, or detection of quiescent virus. We screened 470 adult PLWH in Zambia with neurological symptoms for the presence of EBV DNA in the CSF. We performed quantitative EBV PCR on the CSF and blood. We then performed quantitative EBV DNA PCR on the blood of controls with documented HIV viral suppression without CNS symptoms. The prevalence of EBV DNA in the CSF of patients with CNS symptoms was 28.9% (136/470). EBV DNA positivity was associated with younger age, shorter duration of HIV diagnosis, lower CSF glucose levels, higher CSF protein and white blood cell levels, and a positive CSF Mycobacterium tuberculosis result. The median EBV DNA load was 8000 cps/mL in both the CSF and blood with a range of 2000-2,753,000 cps/mL in the CSF and 1000 to 1,871,000 cps/mL in the blood. Molecular screening of CSF for other possible causes of infection identified Mycobacterium tuberculosis in 30.1% and cytomegalovirus (CMV) in 10.5% of samples. EBV DNA load in the blood and CSF was not associated with mortality. Our results suggest that even though EBV DNA was commonly detected in the CSF of our population, it appears to have limited clinical significance regardless of EBV DNA load.</p>","PeriodicalId":16665,"journal":{"name":"Journal of NeuroVirology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71412669","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":"Disruption of blood-brain barrier: effects of HIV Tat on brain microvascular endothelial cells and tight junction proteins.","authors":"Yuqing Sun, Miaotian Cai, Ying Liang, Yulin Zhang","doi":"10.1007/s13365-023-01179-3","DOIUrl":"10.1007/s13365-023-01179-3","url":null,"abstract":"<p><p>Although the widespread use of antiretroviral therapy (ART) has prolonged the life span of people living with HIV (PLWH), the incidence of HIV-associated neurocognitive disorders (HAND) in PLWH is also gradually increasing, seriously affecting the quality of life for PLWH. However, the pathogenesis of HAND has not been elucidated, which leaves HAND without effective treatment. HIV protein transactivator of transcription (Tat), as an important regulatory protein, is crucial in the pathogenesis of HAND, and its mechanism of HAND has received widespread attention. The blood-brain barrier (BBB) and its cellular component brain microvascular endothelial cells (BMVECs) play a necessary role in protecting the central nervous system (CNS), and their damage associated with Tat is a potential therapeutic target of HAND. In this review, we will study the Tat-mediated damage mechanism of the BBB and present multiple lines of evidence related to BMVEC damage caused by Tat.</p>","PeriodicalId":16665,"journal":{"name":"Journal of NeuroVirology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71412670","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":"Predictors of hippocampal tauopathy in people with and at risk for human immunodeficiency virus infection.","authors":"Sophie Nader, Esma Karlovich, Etty P Cortes, Ricardo Insausti, Gregory Meloni, Michelle Jacobs, John F Crary, Susan Morgello","doi":"10.1007/s13365-023-01181-9","DOIUrl":"10.1007/s13365-023-01181-9","url":null,"abstract":"<p><p>Combination antiretroviral therapy (cART) has extended lifespans of people living with HIV (PWH), increasing both the risk for age-related neuropathologies and the importance of distinguishing effects of HIV and its comorbidities from neurodegenerative disorders. The accumulation of hyperphosphorylated tau (p-tau) in hippocampus is a common degenerative change, with specific patterns of hippocampal subfield vulnerability observed in different disease contexts. Currently, associations between chronic HIV, its comorbidities, and p-tau burden and distribution in the hippocampus are unexplored. We used immunohistochemistry with antibody AT8 to analyze hippocampal p-tau in brain tissues of PWH (n = 71) and HIV negative controls (n = 25), for whom comprehensive clinical data were available. Using a morphology-based neuroanatomical segmentation protocol, we annotated digital slide images to measure percentage p-tau areas in the hippocampus and its subfields. Factors predicting p-tau burden and distribution were identified in univariate analyses, and those with significance at p ≤ 0.100 were advanced to multivariable regression. The patient sample had a mean age of 61.5 years. Age predicted overall hippocampal p-tau burden. Subfield p-tau predictors were for Cornu Ammonis (CA)1, age; for CA2 and subiculum, seizure history; for CA3, seizure history and head trauma; and for CA4/dentate, history of hepatitis C virus (HCV) infection. In this autopsy sample, hippocampal p-tau burden and distribution were not predicted by HIV, viral load, or immunologic status, with viral effects limited to associations between HCV and CA4/dentate vulnerability. Hippocampal p-tau pathologies in cART-era PWH appear to reflect age and comorbidities, but not direct effects of HIV infection.</p>","PeriodicalId":16665,"journal":{"name":"Journal of NeuroVirology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71482728","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":"Immune response to COVID-19 vaccines among people living with human T-cell lymphotropic virus type 1 infection: a retrospective cohort study from Iran.","authors":"Reza Jafarzadeh Esfehani,&nbsp;Zohreh Vahidi,&nbsp;Mohammad Shariati,&nbsp;Arman Mosavat,&nbsp;Azam Shafaei,&nbsp;Maryam Shahi,&nbsp;Houshang Rafatpanah,&nbsp;Hamid Reza Bidkhori,&nbsp;Reza Boostani,&nbsp;Mohammad Reza Hedayati-Moghaddam","doi":"10.1007/s13365-023-01176-6","DOIUrl":"https://doi.org/10.1007/s13365-023-01176-6","url":null,"abstract":"<p><p>The effectiveness of COVID-19 vaccination is still unclear in individuals with underlying diseases such as HTLV-1 infection. This retrospective cohort study aimed to evaluate the humoral response of COVID-19 vaccines among people living with HTLV-1 (PLHTLV) in northeastern Iran. From December 2021 to October 2022, eighty-six HTLV-1⁺ subjects (50 males and 36 females; 47.7 ± 11.2 years) and 90 HTLV-1 seronegative individuals (age- and sex-matched convenient samples) were enrolled. The humoral immune response was evaluated by measuring different COVID-19 Abs in serum samples at least 28 days after receiving 2^nd or 3^rd doses of COVID-19 vaccines. Throughout all three rounds of immunization, Sinopharm was the most commonly used COVID-19 vaccine across all three immunization rounds. Compared to the HTLV-1^- group, a significantly lower frequency of all four Abs activity was observed among PLHTLV:anti-nucleocapsid (66.3% vs 86.7%, p = 0·001), anti-spike (91.9% vs 98.9%, p = 0·027), RBD (90.7% vs 97.8%, p = 0·043), and neutralizing Abs (75.6% vs 95.5%, p < 0·001). Also, the frequency of all Abs in 28 patients with HAM/TSP was higher than that of 58 asymptomatic carriers, although this difference was statistically significant only in the case of anti-spike Abs (p = 0.002). Notably, PLHTLV-vaccinated against COVID-19 demonstrated significantly lower antibody activities, indicating a reduced humoral immune response to COVID-19 vaccines.</p>","PeriodicalId":16665,"journal":{"name":"Journal of NeuroVirology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49691020","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: a retrospective study of the last 12 years in a tertiary-care hospital.","authors":"Jorge Ligero-López, Miguel Ángel Sánchez-Castellano, Iker Falces-Romero, María Dolores Montero-Vega, Julio García-Rodríguez","doi":"10.1007/s13365-023-01158-8","DOIUrl":"10.1007/s13365-023-01158-8","url":null,"abstract":"<p><p>Our study aims to report on the demographic, incidence rate (IR), clinical, and microbiological characteristics of PML patients diagnosed in our tertiary-care hospital over the past 12 years. In this retrospective observational study, we reviewed all requests for JCPyV PCR in CSF from patients with suspected PML. We collected demographic, clinical, and microbiological data of patients diagnosed with PML. Since 2018, real-time quantitative PCR has been used, whereas prior to 2018, samples were sent to our National Reference Center for qualitative diagnosis. Thirteen patients were diagnosed with PML, with 10 of them having a definitive diagnosis and 3 classified as a possible diagnosis with negative PCR results. Eleven patients had advanced HIV, one had non-Hodgkin's lymphoma, and one had systemic lupus erythematosus. Most of the white matter lesions were located at the cerebral level, although the parenchyma and cerebellum were also affected. The most frequent symptoms were behavioral disorders and hemiparesis. The viral load of JCPyV in cerebrospinal fluid was < 1000 copies/mL in three patients. Six patients received compassionate treatment, and all six patients with definitive PML diagnosis died. Although advanced HIV patients were the most affected by PML in our study, it should also be considered in patients with other underlying diseases. While current PCR tests offer high sensitivity and specificity, false negatives can occur. The prognosis of the disease remains poor, and early multidisciplinary diagnosis-including clinical, microbiological, and neuroimaging assessments-remains crucial for improving neurological damage and prognosis.</p>","PeriodicalId":16665,"journal":{"name":"Journal of NeuroVirology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9835207","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}