Pub Date : 2024-10-21DOI: 10.1007/s13365-024-01230-x
Alexandra Balshi, John Dempsey, Jacob A Sloane
We report two patients who developed atypical, disseminated herpes zoster infections while on dimethyl fumarate (DMF) treatment, one with varicella zoster virus (VZV) encephalitis and another with herpes zoster oticus resulting in lasting motor and sensory deficits. We recommend vaccination against VZV prior to DMF initiation be incorporated as standard of care, as ensuring patients are protected against VZV before starting DMF can prevent such severe outcomes.
{"title":"Atypical disseminated herpes zoster infections in patients with demyelinating disease treated with dimethyl fumarate.","authors":"Alexandra Balshi, John Dempsey, Jacob A Sloane","doi":"10.1007/s13365-024-01230-x","DOIUrl":"https://doi.org/10.1007/s13365-024-01230-x","url":null,"abstract":"<p><p>We report two patients who developed atypical, disseminated herpes zoster infections while on dimethyl fumarate (DMF) treatment, one with varicella zoster virus (VZV) encephalitis and another with herpes zoster oticus resulting in lasting motor and sensory deficits. We recommend vaccination against VZV prior to DMF initiation be incorporated as standard of care, as ensuring patients are protected against VZV before starting DMF can prevent such severe outcomes.</p>","PeriodicalId":16665,"journal":{"name":"Journal of NeuroVirology","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468177","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}
Pub Date : 2024-10-18DOI: 10.1007/s13365-024-01234-7
Elena Rita Simula, Somaye Jasemi, Kay Paulus, Leonardo Antonio Sechi
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.
{"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":null,"pages":null},"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}
Pub Date : 2024-10-17DOI: 10.1007/s13365-024-01231-w
Dejan Jakimovski, Robert Zivadinov, Murali Ramanathan, Bianca Weinstock-Guttman, Eleonora Tavazzi, Michael G Dwyer, Niels Bergsland
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.
{"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":null,"pages":null},"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}
Pub Date : 2024-10-04DOI: 10.1007/s13365-024-01229-4
Qiaojuan Zhang, Shao-Chung Hsia, Miguel Martin-Caraballo
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.
{"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":"https://doi.org/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<sup>+</sup> 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<sup>+</sup> 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<sup>+</sup> 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<sup>+</sup> 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<sup>+</sup> channels in order to maintain the transmission of pain information.</p>","PeriodicalId":16665,"journal":{"name":"Journal of NeuroVirology","volume":null,"pages":null},"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}
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.
{"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":"https://doi.org/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":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-08-19","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}
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.
{"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":"https://doi.org/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":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-08-18","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}
Pub Date : 2024-08-18DOI: 10.1007/s13365-024-01226-7
William Clark, Matthew Tanti, Ismail Azzam, Fiona McGill, Maruthi Vinjam
Demyelinating central nervous system (CNS) disorders are a diverse group of conditions characterised by damage to the myelin sheath. These include not only primary autoimmune disorders such as multiple sclerosis (MS) or neuromyelitis optica spectrum disorder (NMOSD), but secondary demyelinating conditions caused by infection and neoplasm, where immunosuppressive therapy may worsen the condition or delay definitive treatment. We describe a young man with an unusual presentation of CNS demyelinating disease associated with HIV infection and positive syphilis serology. MRI brain and spine showed a demyelinating tumefactive lesion accompanied by longitudinal extensive transverse myelitis, and we initially suspected NMOSD. However anti-aquaporin 4 antibodies were negative, going against a diagnosis of NMOSD and he then tested positive for HIV which led us to consider TB myelitis, neurosyphilis and HIV vacuolar myelopathy. He was commenced on highly active retroviral therapy and treated with steroids and immunosuppression. He did not respond to treatment as expected so a brain biopsy was required to narrow the differential. Brain biopsy initially raised the possibility of progressive multifocal leukoencephalopathy which is associated with infection with the John Cunningham (JC) virus. Ultimately JC Virus PCR on the biopsy was negative, the final report suggesting nonspecific active chronic inflammation. We detail his clinical course and the diagnostic challenges along the way.
脱髓鞘性中枢神经系统(CNS)疾病是一组以髓鞘受损为特征的多种疾病。这些疾病不仅包括原发性自身免疫性疾病,如多发性硬化症(MS)或神经脊髓炎视网膜频谱紊乱症(NMOSD),还包括由感染和肿瘤引起的继发性脱髓鞘疾病,在这些疾病中,免疫抑制疗法可能会加重病情或延误最终治疗。我们描述了一名中枢神经系统脱髓鞘疾病的年轻男子,他的症状与艾滋病病毒感染和梅毒血清学阳性有关,表现不寻常。脑部和脊柱核磁共振成像(MRI)显示脱髓鞘瘤样病变,伴有纵向广泛横贯性脊髓炎,我们起初怀疑是NMOSD。然而,抗喹诺酮 4 抗体呈阴性,这与 NMOSD 的诊断相悖,随后他的 HIV 检测呈阳性,这让我们不得不考虑结核性脊髓炎、神经梅毒和 HIV 空泡性脊髓病。他开始接受高活性逆转录病毒疗法,并接受类固醇和免疫抑制治疗。他对治疗的反应不如预期,因此需要进行脑活检以缩小鉴别范围。脑活检最初提出了进行性多灶性白质脑病的可能性,这与感染约翰-坎宁安(JC)病毒有关。最终,活组织检查的 JC 病毒 PCR 呈阴性,最终报告显示为非特异性活动性慢性炎症。我们将详细介绍他的临床病程和诊断过程中遇到的挑战。
{"title":"Unusual demyelinating disease in a patient with HIV infection.","authors":"William Clark, Matthew Tanti, Ismail Azzam, Fiona McGill, Maruthi Vinjam","doi":"10.1007/s13365-024-01226-7","DOIUrl":"https://doi.org/10.1007/s13365-024-01226-7","url":null,"abstract":"<p><p>Demyelinating central nervous system (CNS) disorders are a diverse group of conditions characterised by damage to the myelin sheath. These include not only primary autoimmune disorders such as multiple sclerosis (MS) or neuromyelitis optica spectrum disorder (NMOSD), but secondary demyelinating conditions caused by infection and neoplasm, where immunosuppressive therapy may worsen the condition or delay definitive treatment. We describe a young man with an unusual presentation of CNS demyelinating disease associated with HIV infection and positive syphilis serology. MRI brain and spine showed a demyelinating tumefactive lesion accompanied by longitudinal extensive transverse myelitis, and we initially suspected NMOSD. However anti-aquaporin 4 antibodies were negative, going against a diagnosis of NMOSD and he then tested positive for HIV which led us to consider TB myelitis, neurosyphilis and HIV vacuolar myelopathy. He was commenced on highly active retroviral therapy and treated with steroids and immunosuppression. He did not respond to treatment as expected so a brain biopsy was required to narrow the differential. Brain biopsy initially raised the possibility of progressive multifocal leukoencephalopathy which is associated with infection with the John Cunningham (JC) virus. Ultimately JC Virus PCR on the biopsy was negative, the final report suggesting nonspecific active chronic inflammation. We detail his clinical course and the diagnostic challenges along the way.</p>","PeriodicalId":16665,"journal":{"name":"Journal of NeuroVirology","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142000191","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}
Pub Date : 2024-08-12DOI: 10.1007/s13365-024-01225-8
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
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.
在少数群体中,APOE 对 HIV 和 HCV 病程、认知和记忆的影响还未得到充分研究。本研究在考虑 HCV 和 HIV 血清阳性反应的同时,考察了 APOE ε4 携带者的认知和抑郁指标得分是否存在差异,以及这些指标是否受药物使用的影响。一项回顾性分析研究了迈阿密成人艾滋病研究(MASH)队列中参与者(n = 493)的认知和心理数据。对银行血样进行了 APOE 基因分型。采用多元线性回归来检验感染 HIV 和/或 HCV 的参与者与未感染 HIV 和/或 HCV 的参与者之间的差异,以及 APOE ε4 基因型的差异。使用大麻的丙肝病毒 APOE ε4 携带者的抑郁评分高于非ε4 携带者,而不使用大麻者的抑郁症状较少。对使用可卡因、鸦片和大麻的情况进行调整后,感染了 HCV 的 APOE ε4 携带者的认知得分高于非 ε4 携带者。在感染艾滋病毒的参与者中,APOE ε4携带者与非ε4携带者在认知和抑郁测量上的得分并无差异,使用药物也不会缓和这种关系。这项研究是首次对按 APOE 基因型分层的 HIV 和/或 HCV 感染者中使用药物作为认知和抑郁的调节因素进行研究。研究结果支持进一步开展研究,评估 1) 与药物使用相关的 APOE 基因型对认知功能领域的影响的频率和持续时间,以及 2) 药物使用对感染 HIV 和 HCV、HIV 或 HCV 的成年人的认知和抑郁结果的影响。
{"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":null,"pages":null},"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}
Pub Date : 2024-06-29DOI: 10.1007/s13365-024-01223-w
Brooks I Mitchell, Isabelle E Yazel Eiser, Kalpana J Kallianpur, Louie Mar Gangcuangco, Dominic C Chow, Lishomwa C Ndhlovu, Robert Paul, Cecilia M Shikuma
Background: HIV-associated neurocognitive disorders (HAND) is hypothesized to be a result of myeloid cell-induced neuro-inflammation in the central nervous system that may be initiated in the periphery, but the contribution of peripheral T cells in HAND pathogenesis remains poorly understood.
Methods: We assessed markers of T cell activation (HLA-DR + CD38+), immunosenescence (CD57 + CD28-), and immune-exhaustion (TIM-3, PD-1 and TIGIT) as well as monocyte subsets (classical, intermediate, and non-classical) by flow cytometry in peripheral blood derived from individuals with HIV on long-term stable anti-retroviral therapy (ART). Additionally, normalized neuropsychological (NP) composite test z-scores were obtained and regional brain volumes were assessed by magnetic resonance imaging (MRI). Relationships between proportions of immune phenotypes (of T-cells and monocytes), NP z-scores, and brain volumes were analyzed using Pearson correlations and multiple linear regression models.
Results: Of N = 51 participants, 84.3% were male, 86.3% had undetectable HIV RNA < 50 copies/ml, median age was 52 [47, 57] years and median CD4 T cell count was 479 [376, 717] cells/uL. Higher CD4 T cells expressing PD-1 + and/or TIM-3 + were associated with lower executive function and working memory and higher CD8 T cells expressing PD-1+ and/or TIM-3+ were associated with reduced brain volumes in multiple regions (putamen, nucleus accumbens, cerebellar cortex, and subcortical gray matter). Furthermore, higher single or dual frequencies of PD-1 + and TIM-3 + expressing CD4 and CD8 T-cells correlated with higher CD16 + monocyte numbers.
Conclusions: This study reinforces evidence that T cells, particularly those with immune exhaustion phenotypes, are associated with neurocognitive impairment and brain atrophy in people living with HIV on ART. Relationships revealed between T-cell immune exhaustion and inflammatory in CD16+ monocytes uncover interrelated cellular processes likely involved in the immunopathogenesis of HAND.
背景:HIV相关神经认知障碍(HAND)被认为是中枢神经系统髓系细胞诱导神经炎症的结果,这种炎症可能从外周开始,但外周T细胞在HAND发病机制中的作用仍鲜为人知:我们通过流式细胞术评估了长期稳定接受抗逆转录病毒疗法(ART)的 HIV 感染者外周血中的 T 细胞活化(HLA-DR + CD38+)、免疫衰老(CD57 + CD28-)和免疫耗竭(TIM-3、PD-1 和 TIGIT)标志物以及单核细胞亚群(经典、中间和非经典)。此外,还获得了归一化神经心理学(NP)综合测试 z 分数,并通过磁共振成像(MRI)评估了区域脑容量。使用皮尔逊相关性和多元线性回归模型分析了免疫表型(T 细胞和单核细胞)比例、NP z 分数和脑容量之间的关系:结果:在 N = 51 名参与者中,84.3% 为男性,86.3% 检测不到 HIV RNA + 和/或 TIM-3+ 与多个区域(普鲁门、伏隔核、小脑皮质和皮质下灰质)的脑容量减少有关。此外,表达 PD-1 + 和 TIM-3 + 的 CD4 和 CD8 T 细胞的单一或双重频率较高与 CD16 + 单核细胞数量较高相关:这项研究进一步证明了T细胞,尤其是具有免疫耗竭表型的T细胞,与接受抗逆转录病毒疗法的艾滋病病毒感染者的神经认知障碍和脑萎缩有关。T细胞免疫耗竭与CD16+单核细胞炎症之间的关系揭示了可能参与HAND免疫发病机制的相互关联的细胞过程。
{"title":"Dynamics of peripheral T cell exhaustion and monocyte subpopulations in neurocognitive impairment and brain atrophy in chronic HIV infection.","authors":"Brooks I Mitchell, Isabelle E Yazel Eiser, Kalpana J Kallianpur, Louie Mar Gangcuangco, Dominic C Chow, Lishomwa C Ndhlovu, Robert Paul, Cecilia M Shikuma","doi":"10.1007/s13365-024-01223-w","DOIUrl":"https://doi.org/10.1007/s13365-024-01223-w","url":null,"abstract":"<p><strong>Background: </strong>HIV-associated neurocognitive disorders (HAND) is hypothesized to be a result of myeloid cell-induced neuro-inflammation in the central nervous system that may be initiated in the periphery, but the contribution of peripheral T cells in HAND pathogenesis remains poorly understood.</p><p><strong>Methods: </strong>We assessed markers of T cell activation (HLA-DR + CD38+), immunosenescence (CD57 + CD28-), and immune-exhaustion (TIM-3, PD-1 and TIGIT) as well as monocyte subsets (classical, intermediate, and non-classical) by flow cytometry in peripheral blood derived from individuals with HIV on long-term stable anti-retroviral therapy (ART). Additionally, normalized neuropsychological (NP) composite test z-scores were obtained and regional brain volumes were assessed by magnetic resonance imaging (MRI). Relationships between proportions of immune phenotypes (of T-cells and monocytes), NP z-scores, and brain volumes were analyzed using Pearson correlations and multiple linear regression models.</p><p><strong>Results: </strong>Of N = 51 participants, 84.3% were male, 86.3% had undetectable HIV RNA < 50 copies/ml, median age was 52 [47, 57] years and median CD4 T cell count was 479 [376, 717] cells/uL. Higher CD4 T cells expressing PD-1 + and/or TIM-3 + were associated with lower executive function and working memory and higher CD8 T cells expressing PD-1<sup>+</sup> and/or TIM-3<sup>+</sup> were associated with reduced brain volumes in multiple regions (putamen, nucleus accumbens, cerebellar cortex, and subcortical gray matter). Furthermore, higher single or dual frequencies of PD-1 + and TIM-3 + expressing CD4 and CD8 T-cells correlated with higher CD16 + monocyte numbers.</p><p><strong>Conclusions: </strong>This study reinforces evidence that T cells, particularly those with immune exhaustion phenotypes, are associated with neurocognitive impairment and brain atrophy in people living with HIV on ART. Relationships revealed between T-cell immune exhaustion and inflammatory in CD16<sup>+</sup> monocytes uncover interrelated cellular processes likely involved in the immunopathogenesis of HAND.</p>","PeriodicalId":16665,"journal":{"name":"Journal of NeuroVirology","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141468752","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}
Pub Date : 2024-06-27DOI: 10.1007/s13365-024-01218-7
Laura da Silva Siqueira, Felipe Valle Fortes Rodrigues, Ângela Zanatta, João Ismael Budelon Gonçalves, Isadora Machado Ghilardi, Allan Marinho Alcará, Nicole Bernd Becker, Giulia Pinzetta, Gabriele Zanirati, Bruno Maestri Abrianos Becker, Helena Scartassini Erwig, Jaderson Costa da Costa, Daniel Rodrigo Marinowic
After the Zika virus (ZIKV) epidemic in Brazil, ZIKV infections were linked to damage to the central nervous system (CNS) and congenital anomalies. Due to the virus's ability to cross the placenta and reach brain tissue, its effects become severe, leading to Congenital Zika Syndrome (CZS) and resulting in neuroinflammation, microglial activation, and secretion of neurotoxic factors. The presence of ZIKV triggers an inadequate fetal immune response, as the fetus only has the protection of maternal antibodies of the Immunoglobulin G (IgG) class, which are the only antibodies capable of crossing the placenta. Because of limited understanding regarding the long term consequences of ZIKV infection and the involvement of maternal antibodies, this study sought to assess the impact of the ZIKV + IgG⁺complex on murine microglial cells. The cells were exposed to ZIKV, IgG antibodies, and the ZIKV + IgG⁺complex for 24 and 72 h. Treatment-induced cytotoxic effects were evaluated using the cell viability assay, oxidative stress, and mitochondrial membrane potential. The findings indicated that IgG antibodies exhibit cytotoxic effects on microglia, whether alone or in the presence of ZIKV, leading to compromised cell viability, disrupted mitochondrial membrane potential, and heightened oxidative damage. Our conclusion is that IgG antibodies exert detrimental effects on microglia, triggering their activation and potentially disrupting the creation of a neurotoxic environment. Moreover, the presence of antibodies may correlate with an elevated risk of ZIKV-induced neuroinflammation, contributing to long-term CNS damage.
{"title":"Evaluation of the effects of the Zika Virus-Immunoglobulin G<sup>+</sup> complex on murine microglial cells.","authors":"Laura da Silva Siqueira, Felipe Valle Fortes Rodrigues, Ângela Zanatta, João Ismael Budelon Gonçalves, Isadora Machado Ghilardi, Allan Marinho Alcará, Nicole Bernd Becker, Giulia Pinzetta, Gabriele Zanirati, Bruno Maestri Abrianos Becker, Helena Scartassini Erwig, Jaderson Costa da Costa, Daniel Rodrigo Marinowic","doi":"10.1007/s13365-024-01218-7","DOIUrl":"https://doi.org/10.1007/s13365-024-01218-7","url":null,"abstract":"<p><p>After the Zika virus (ZIKV) epidemic in Brazil, ZIKV infections were linked to damage to the central nervous system (CNS) and congenital anomalies. Due to the virus's ability to cross the placenta and reach brain tissue, its effects become severe, leading to Congenital Zika Syndrome (CZS) and resulting in neuroinflammation, microglial activation, and secretion of neurotoxic factors. The presence of ZIKV triggers an inadequate fetal immune response, as the fetus only has the protection of maternal antibodies of the Immunoglobulin G (IgG) class, which are the only antibodies capable of crossing the placenta. Because of limited understanding regarding the long term consequences of ZIKV infection and the involvement of maternal antibodies, this study sought to assess the impact of the ZIKV + IgG⁺complex on murine microglial cells. The cells were exposed to ZIKV, IgG antibodies, and the ZIKV + IgG⁺complex for 24 and 72 h. Treatment-induced cytotoxic effects were evaluated using the cell viability assay, oxidative stress, and mitochondrial membrane potential. The findings indicated that IgG antibodies exhibit cytotoxic effects on microglia, whether alone or in the presence of ZIKV, leading to compromised cell viability, disrupted mitochondrial membrane potential, and heightened oxidative damage. Our conclusion is that IgG antibodies exert detrimental effects on microglia, triggering their activation and potentially disrupting the creation of a neurotoxic environment. Moreover, the presence of antibodies may correlate with an elevated risk of ZIKV-induced neuroinflammation, contributing to long-term CNS damage.</p>","PeriodicalId":16665,"journal":{"name":"Journal of NeuroVirology","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141457515","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}