Journal of NeuroVirology最新文献

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Correction: GP120 and tenofovir alafenamide alter cannabinoid receptor 1 expression in hippocampus of mice. 更正:GP120 和替诺福韦-阿拉非酰胺会改变小鼠海马中大麻素受体 1 的表达。
IF 3.2 4区 医学
Journal of NeuroVirology Pub Date : 2024-02-01 DOI: 10.1007/s13365-023-01192-6
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}
引用次数: 0
Understanding the link between neurotropic viruses, BBB permeability, and MS pathogenesis. 了解神经性病毒、BBB 通透性和多发性硬化症发病机制之间的联系。
IF 3.2 4区 医学
Journal of NeuroVirology Pub Date : 2024-02-01 Epub Date: 2024-01-08 DOI: 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}
引用次数: 0
HIV-1 mRNA knockdown with CRISPR/CAS9 enhances neurocognitive function. 用 CRISPR/CAS9 敲除 HIV-1 mRNA 可增强神经认知功能。
IF 3.2 4区 医学
Journal of NeuroVirology Pub Date : 2024-02-01 Epub Date: 2024-02-14 DOI: 10.1007/s13365-024-01193-z
Kristen A McLaurin, Hailong Li, Kamel Khalili, Charles F Mactutus, Rosemarie M Booze
{"title":"HIV-1 mRNA knockdown with CRISPR/CAS9 enhances neurocognitive function.","authors":"Kristen A McLaurin, Hailong Li, Kamel Khalili, Charles F Mactutus, Rosemarie M Booze","doi":"10.1007/s13365-024-01193-z","DOIUrl":"10.1007/s13365-024-01193-z","url":null,"abstract":"<p><p>Mixed glia are infiltrated with HIV-1 virus early in the course of infection leading to the development of a persistent viral reservoir in the central nervous system. Modification of the HIV-1 genome using gene editing techniques, including CRISPR/Cas9, has shown great promise towards eliminating HIV-1 viral reservoirs; whether these techniques are capable of removing HIV-1 viral proteins from mixed glia, however, has not been systematically evaluated. Herein, the efficacy of adeno-associated virus 9 (AAV9)-CRISPR/Cas9 gene editing for eliminating HIV-1 messenger RNA (mRNA) from cortical mixed glia was evaluated in vitro and in vivo. In vitro, a within-subjects experimental design was utilized to treat mixed glia isolated from neonatal HIV-1 transgenic (Tg) rats with varying doses (0, 0.9, 1.8, 2.7, 3.6, 4.5, or 5.4 µL corresponding to a physical titer of 0, 4.23 × 10<sup>9</sup>, 8.46 × 10<sup>9</sup>, 1.269 × 10<sup>10</sup>, 1.692 × 10<sup>10</sup>, 2.115 × 10<sup>10</sup>, and 2.538 × 10<sup>10</sup> gc/µL) of CRISPR/Cas9 for 72 h. Dose-dependent decreases in the number of HIV-1 mRNA, quantified using an innovative in situ hybridization technique, were observed in a subset (i.e., n = 5 out of 8) of primary mixed glia. In vivo, HIV-1 Tg rats were retro-orbitally inoculated with CRISPR/Cas9 for two weeks, whereby treatment resulted in profound excision (i.e., approximately 53.2%) of HIV-1 mRNA from the medial prefrontal cortex. Given incomplete excision of the HIV-1 viral genome, the clinical relevance of HIV-1 mRNA knockdown for eliminating neurocognitive impairments was evaluated via examination of temporal processing, a putative neurobehavioral mechanism underlying HIV-1-associated neurocognitive disorders (HAND). Indeed, treatment with CRISPR/Cas9 protractedly, albeit not permanently, restored the developmental trajectory of temporal processing. Proof-of-concept studies, therefore, support the susceptibility of mixed glia to gene editing and the potential of CRISPR/Cas9 to serve as a novel therapeutic strategy for HAND, even in the absence of full viral eradication.</p>","PeriodicalId":16665,"journal":{"name":"Journal of NeuroVirology","volume":" ","pages":"71-85"},"PeriodicalIF":3.2,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11035469/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139735475","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}
引用次数: 0
Correction to: Reduced neuronal population in the dorsolateral prefrontal cortex in infant macaques infected with simian immunodeficiency virus (SIV). 更正:感染猿类免疫缺陷病毒 (SIV) 的猕猴幼年背外侧前额叶皮层神经元数量减少。
IF 3.2 4区 医学
Journal of NeuroVirology Pub Date : 2024-02-01 DOI: 10.1007/s13365-023-01185-5
Alexandra Haddad, Brittany Voth, Janiya Brooks, Melanie Swang, Heather Carryl, Norah Algarzae, Shane Taylor, Camryn Parker, Koen K A Van Rompay, Kristina De Paris, Mark W Burke
{"title":"Correction to: Reduced neuronal population in the dorsolateral prefrontal cortex in infant macaques infected with simian immunodeficiency virus (SIV).","authors":"Alexandra Haddad, Brittany Voth, Janiya Brooks, Melanie Swang, Heather Carryl, Norah Algarzae, Shane Taylor, Camryn Parker, Koen K A Van Rompay, Kristina De Paris, Mark W Burke","doi":"10.1007/s13365-023-01185-5","DOIUrl":"10.1007/s13365-023-01185-5","url":null,"abstract":"","PeriodicalId":16665,"journal":{"name":"Journal of NeuroVirology","volume":" ","pages":"100"},"PeriodicalIF":3.2,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11035453/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139672047","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}
引用次数: 0
Reactivation of varicella zoster virus following trigeminal schwannoma resection 三叉神经裂孔瘤切除术后水痘带状疱疹病毒再活化
IF 3.2 4区 医学
Journal of NeuroVirology Pub Date : 2023-12-14 DOI: 10.1007/s13365-023-01189-1
Singh Deepak Kumar, Sinha Kshitij, Singh Rakesh Kumar, Yadav Kuldeep, Kaif Mohammad, Chand Vipin Kumar, Singh Nirbhay
{"title":"Reactivation of varicella zoster virus following trigeminal schwannoma resection","authors":"Singh Deepak Kumar, Sinha Kshitij, Singh Rakesh Kumar, Yadav Kuldeep, Kaif Mohammad, Chand Vipin Kumar, Singh Nirbhay","doi":"10.1007/s13365-023-01189-1","DOIUrl":"https://doi.org/10.1007/s13365-023-01189-1","url":null,"abstract":"<p>Varicella zoster is found exclusively in humans. Infected people with this virus result in chickenpox followed by dormant virus within neural ganglia. This dormant virus, once activated, may affect any ganglia or nerves of the body but most commonly involves the thoracic, cervical and trigeminal nerves in decreasing order of frequency. We review three such cases in which manipulation of the trigeminal ganglion resulted in reactivation of varicella at homologous operative sites. Each patient underwent surgeries in which the trigeminal ganglion was manipulated for the resection of trigeminal schwannoma under a microscope through various approaches. All three patients developed reactivation of varicella at homologous operative sites. A thorough history of chickenpox infection should be taken in patients who are undergoing surgeries for trigeminal pathology. Early diagnosis should be made once any vesicular lesions are seen with prompt treatment. Reassurance and counselling are necessary in these patients. If possible, prophylaxis may be started in all such patients. Further studies are warranted to determine the exact cause of reactivation.</p>","PeriodicalId":16665,"journal":{"name":"Journal of NeuroVirology","volume":"17 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138628415","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}
引用次数: 0
Genetic polymorphisms in innate immunity genes influence predisposition to tick-borne encephalitis. 先天免疫基因的遗传多态性影响蜱传脑炎的易感性。
IF 3.2 4区 医学
Journal of NeuroVirology Pub Date : 2023-12-01 Epub Date: 2023-10-28 DOI: 10.1007/s13365-023-01182-8
Andrea Fortova, Andrey V Barkhash, Martina Pychova, Lenka Krbkova, Martin Palus, Jiri Salat, Daniel Ruzek
{"title":"Genetic polymorphisms in innate immunity genes influence predisposition to tick-borne encephalitis.","authors":"Andrea Fortova, Andrey V Barkhash, Martina Pychova, Lenka Krbkova, Martin Palus, Jiri Salat, Daniel Ruzek","doi":"10.1007/s13365-023-01182-8","DOIUrl":"10.1007/s13365-023-01182-8","url":null,"abstract":"<p><p>Tick-borne encephalitis (TBE) is a neuroviral disease that ranges in severity from a mild febrile illness to a severe and life-threatening meningoencephalitis or encephalomyelitis. There is increasing evidence that susceptibility to tick-borne encephalitis virus (TBEV)-induced disease and its severity are largely influenced by host genetic factors, in addition to other virus- and host-related factors. In this study, we investigated the contribution of selected single nucleotide polymorphisms (SNPs) in innate immunity genes to predisposition to TBE in humans. More specifically, we investigated a possible association between SNPs rs304478 and rs303212 in the gene Interferon Induced Protein With Tetratricopeptide Repeats 1 (IFIT1), rs7070001 and rs4934470 in the gene Interferon Induced Protein With Tetratricopeptide Repeats 2 (IFIT2), and RIG-I (Retinoic acid-inducible gene I) encoding gene DDX58 rs311795343, rs10813831, rs17217280 and rs3739674 SNPs with predisposition to TBE in population of the Czech Republic, where TBEV is highly endemic. Genotypic and allelic frequencies for these SNPs were analyzed in 247 nonimmunized TBE patients and compared with 204 control subjects. The analysis showed an association of IFIT1 rs304478 SNP and DDX58 rs3739674 and rs17217280 SNPs with predisposition to TBE in the Czech population indicating novel risk factors for clinical TBE but not for disease severity. These results also highlight the role of innate immunity genes in TBE pathogenesis.</p>","PeriodicalId":16665,"journal":{"name":"Journal of NeuroVirology","volume":" ","pages":"699-705"},"PeriodicalIF":3.2,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10794283/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66784000","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}
引用次数: 0
Is there a connection between neurocognitive profile in treatment naïve non-cirrhotic HCV patients and level of systemic inflammation? 治疗幼稚的非肝硬化HCV患者的神经认知特征与全身炎症水平之间有联系吗?
IF 3.2 4区 医学
Journal of NeuroVirology Pub Date : 2023-12-01 Epub Date: 2023-11-10 DOI: 10.1007/s13365-023-01184-6
Maja Ružić, Natalija Rajić, Željka Nikolašević, Aleksandar Spasić, Maria Pete, Vojislava Bugarski Ignjatović
{"title":"Is there a connection between neurocognitive profile in treatment naïve non-cirrhotic HCV patients and level of systemic inflammation?","authors":"Maja Ružić, Natalija Rajić, Željka Nikolašević, Aleksandar Spasić, Maria Pete, Vojislava Bugarski Ignjatović","doi":"10.1007/s13365-023-01184-6","DOIUrl":"10.1007/s13365-023-01184-6","url":null,"abstract":"<p><p>Hepatitis C virus (HCV) infection is a progressive, systemic disease which leads to the development of end-stage liver disease. In 70% of patients, HCV infection is followed by the development of extrahepatic manifestations (EHM). A common EHM is HCV associated neurocognitive disorder (HCV-AND), characterized by neuropsychological changes in attention, working memory, psychomotor speed, executive function, verbal learning, and recall. The aim of this study is to examine the correlation between the neurocognitive profile and routine, available laboratory parameters of inflammation, liver function tests, grade of liver fibrosis, and clinical and laboratory parameters of mixed cryoglobulinemia in treatment naïve non-cirrhotic HCV patients. This is a single-center exploratory study in which we examined 38 HCV + treatment naïve patients. The complete blood count and hematological parameters of systemic inflammation, liver function tests, biopsy confirmed grade of liver fibrosis, and clinical and laboratory parameters of mixed cryoglobulinemia caused by chronic HCV infection were observed. In the study, we used a battery of neuropsychological tests assessing multiple cognitive domains: executive functions, verbal fluency, delayed memory, working memory and learning, and one measure for visuo-constructive performance. Before the Bonferroni correction for multiple comparisons, the results show significant correlations between the scores in the neurocognitive variables and the single measures of inflammation, liver function parameters, and mixed cryoglobulinemia. It has not found a statistically significant correlation between systemic inflammation and neurocognitive variables. After the Bonferroni adjustment, no correlations remained significant. Certainly, the obtained results can be a recommendation for additional validation through future research.</p>","PeriodicalId":16665,"journal":{"name":"Journal of NeuroVirology","volume":" ","pages":"723-730"},"PeriodicalIF":3.2,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72014571","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}
引用次数: 0
The relationship between synaptodendritic neuropathology and HIV-associated neurocognitive disorders is moderated by cognitive reserve. 突触树突神经病理学和HIV相关神经认知障碍之间的关系由认知储备调节。
IF 3.2 4区 医学
Journal of NeuroVirology Pub Date : 2023-12-01 Epub Date: 2023-11-09 DOI: 10.1007/s13365-023-01177-5
Arin Fisher, David J Moore, Andrew J Levine, Eliezer Masliah, Ben Gouaux, Virawudh Soontornniyomkij, Scott Letendre, Erin E Sundermann
{"title":"The relationship between synaptodendritic neuropathology and HIV-associated neurocognitive disorders is moderated by cognitive reserve.","authors":"Arin Fisher, David J Moore, Andrew J Levine, Eliezer Masliah, Ben Gouaux, Virawudh Soontornniyomkij, Scott Letendre, Erin E Sundermann","doi":"10.1007/s13365-023-01177-5","DOIUrl":"10.1007/s13365-023-01177-5","url":null,"abstract":"<p><p>We examined whether cognitive reserve moderated the relationship between neurodegeneration and cognition in 67 postmortem persons with HIV (PWH) who were cognitively assessed within 1 year of death. Cognitive reserve was measured via the Wide Range Achievement Test-4 reading subtest (WRAT4). Synaptodendritic neurodegeneration was based on densities of synaptophysin and microtubule-associated protein 2 immunohistochemical reactivity in frontal cortex, and categorized as minimal, moderate, or severe (tertile-split). T-Scores from 15 cognitive tests were averaged into a global cognitive T-score. Among those with low cognitive reserve (based on WRAT4 median split), the moderate neurodegeneration group showed cognition that was poorer than the minimal neurodegeneration group and comparable to the severe neurodegeneration group. Among those with high cognitive reserve, the moderate neurodegeneration group showed cognition comparable to the minimal neurodegeneration group and better than the severe neurodegeneration group. High cognitive reserve may buffer against cognitive impairment among PWH with moderate, but not severe, neurodegeneration.</p>","PeriodicalId":16665,"journal":{"name":"Journal of NeuroVirology","volume":" ","pages":"713-722"},"PeriodicalIF":3.2,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71521809","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}
引用次数: 0
Correction: Performance of the national institute of infectious diseases disability scale in HTLV-1-associated myelopathy/tropical spastic paraparesis. 更正:htlv -1相关脊髓病/热带痉挛性截瘫的国家传染病研究所残疾量表的表现。
IF 3.2 4区 医学
Journal of NeuroVirology Pub Date : 2023-12-01 DOI: 10.1007/s13365-023-01188-2
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
{"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":" ","pages":"734"},"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}
引用次数: 0
HSV-1 latency-associated transcript miR-H3 and miR-H4 target STXBP1 and GABBR2 genes. HSV-1 潜伏期相关转录本 miR-H3 和 miR-H4 的靶标是 STXBP1 和 GABBR2 基因。
IF 3.2 4区 医学
Journal of NeuroVirology Pub Date : 2023-12-01 Epub Date: 2023-09-05 DOI: 10.1007/s13365-023-01174-8
Karrar Mahmood Shaker Al-Khfaji, Nika Kooshki Zamani, Ehsan Arefian
{"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":" ","pages":"669-677"},"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}
引用次数: 0
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