scholarly journals Analysis of ALS-related proteins during herpes simplex virus-2 latent infection

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Jorge Rubén Cabrera ◽  
Ignacio Rodríguez-Izquierdo ◽  
José Luis Jiménez ◽  
María Ángeles Muñoz-Fernández
Keyword(s):  
Spinal Cord ◽  
Herpes Simplex ◽  
Latent Infection ◽  
Genetic Alterations ◽  
Leukocyte Infiltration ◽  
Cytoplasmic Inclusions ◽  
Herpes Simplex Viruses ◽  
Protein Levels ◽  
Als Patients ◽  
Related Proteins

Abstract Background Genetics have provided hints on potential molecular pathways involved in neurodegenerative diseases (NDD). However, the number of cases caused exclusively by genetic alterations is low, suggesting an important contribution of environmental factors to NDDs. Among these factors, viruses like herpes simplex viruses (HSV-2), capable of establishing lifelong infections within the nervous system (NS), are being proposed to have a role in NDDs. Despite promising data, there is a significant lack of knowledge on this and an urgent need for more research. Methods We have set up a mouse model to study HSV latency and its associated neuroinflammation in the spinal cord. The goal of this model was to observe neuroinflammatory changes caused by HSV latent infections, and if those changes were similar to alterations observed in the spinal cord of amyotrophic lateral sclerosis (ALS) patients. Results In infected spinal cords, we have observed a strong leukocyte infiltration and a severe alteration of microglia close to motor neurons. We have also analyzed ALS-related proteins: we have not found changes in TDP-43 and Fus in neurons, but interestingly, we have found decreased protein levels of C9orf72, of which coding gene is severely altered in some familial forms of ALS and is critical for microglia homeostasis. Conclusions Latent infection of HSV in the spinal cord showed altered microglia and leukocyte infiltration. These inflammatory features resembled to those observed in the spinal cord of ALS patients. No changes mimicking ALS neuropathology, such as TDP-43 cytoplasmic inclusions, were found in infected spinal cords, but a decrease in protein levels of C9orf72 was observed. Then, further studies should be required to determine whether HSV-2 has a role in ALS.

scholarly journals Multifunctional Non-Coding RNAs Mediate Latent Infection and Recurrence of Herpes Simplex Viruses

2021 ◽  
Vol Volume 14 ◽  
pp. 5335-5349
Author(s):  
Ying Zhang ◽  
Li-Si Zeng ◽  
Juan Wang ◽  
Wen-Qi Cai ◽  
Weiwen Cui ◽  
...  
Keyword(s):  
Herpes Simplex ◽  
Latent Infection ◽  
Herpes Simplex Viruses ◽  
Non Coding Rnas

scholarly journals Numerous Conserved and Divergent MicroRNAs Expressed by Herpes Simplex Viruses 1 and 2

2010 ◽  
Vol 84 (9) ◽  
pp. 4659-4672 ◽  
Author(s):  
Igor Jurak ◽  
Martha F. Kramer ◽  
Joseph C. Mellor ◽  
Alison L. van Lint ◽  
Frederick P. Roth ◽  
...  
Keyword(s):  
Herpes Simplex ◽  
Latent Infection ◽  
Massively Parallel Sequencing ◽  
Mirna Family ◽  
Productive Infection ◽  
Seed Region ◽  
Herpes Simplex Viruses ◽  
Functional Analog ◽  
Host Genes ◽  
Hsv 1

ABSTRACT Certain viruses use microRNAs (miRNAs) to regulate the expression of their own genes, host genes, or both. Previous studies have identified a limited number of miRNAs expressed by herpes simplex viruses 1 and 2 (HSV-1 and -2), some of which are conserved between these two viruses. To more comprehensively analyze the miRNAs expressed by HSV-1 or HSV-2 during productive and latent infection, we applied a massively parallel sequencing approach. We were able to identify 16 and 17 miRNAs expressed by HSV-1 and HSV-2, respectively, including all previously known species, and a number of previously unidentified virus-encoded miRNAs. The genomic positions of most miRNAs encoded by these two viruses are within or proximal to the latency-associated transcript region. Nine miRNAs are conserved in position and/or sequence, particularly in the seed region, between these two viruses. Interestingly, we did not detect an HSV-2 miRNA homolog of HSV-1 miR-H1, which is highly expressed during productive infection, but we did detect abundant expression of miR-H6, whose seed region is conserved with HSV-1 miR-H1 and might represent a functional analog. We also identified a highly conserved miRNA family arising from the viral origins of replication. In addition, we detected several pairs of complementary miRNAs and we found miRNA-offset RNAs (moRs) arising from the precursors of HSV-1 and HSV-2 miR-H6 and HSV-2 miR-H4. Our results reveal elements of miRNA conservation and divergence that should aid in identifying miRNA functions.

scholarly journals D-dopachrome tautomerase activates COX2/PGE2 pathway of astrocytes to mediate inflammation following spinal cord injury

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Huiyuan Ji ◽  
Yuxin Zhang ◽  
Chen Chen ◽  
Hui Li ◽  
Bingqiang He ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Signal Pathways ◽  
Post Injury ◽  
Dopachrome Tautomerase ◽  
Protein Levels ◽  
Cytokines And Chemokines ◽  
Cord Injury ◽  
Mitogen Activated Protein ◽  
Spinal Cord Contusion

Abstract Background Astrocytes are the predominant glial cell type in the central nervous system (CNS) that can secrete various cytokines and chemokines mediating neuropathology in response to danger signals. D-dopachrome tautomerase (D-DT), a newly described cytokine and a close homolog of macrophage migration inhibitory factor (MIF) protein, has been revealed to share an overlapping function with MIF in some ways. However, its cellular distribution pattern and mediated astrocyte neuropathological function in the CNS remain unclear. Methods A contusion model of the rat spinal cord was established. The protein levels of D-DT and PGE2 synthesis-related proteinase were assayed by Western blot and immunohistochemistry. Primary astrocytes were stimulated by different concentrations of D-DT in the presence or absence of various inhibitors to examine relevant signal pathways. The post-injury locomotor functions were assessed using the Basso, Beattie, and Bresnahan (BBB) locomotor scale. Results D-DT was inducibly expressed within astrocytes and neurons, rather than in microglia following spinal cord contusion. D-DT was able to activate the COX2/PGE2 signal pathway of astrocytes through CD74 receptor, and the intracellular activation of mitogen-activated protein kinases (MAPKs) was involved in the regulation of D-DT action. The selective inhibitor of D-DT was efficient in attenuating D-DT-induced astrocyte production of PGE2 following spinal cord injury, which contributed to the improvement of locomotor functions. Conclusion Collectively, these data reveal a novel inflammatory activator of astrocytes following spinal cord injury, which might be beneficial for the development of anti-inflammation drug in neuropathological CNS.

scholarly journals Antimicrobial, Antioxidant, and Cytotoxic Activities of Juglans regia L. Pellicle Extract

Antibiotics ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 159
Author(s):  
Floriana D’Angeli ◽  
Giuseppe Antonio Malfa ◽  
Adriana Garozzo ◽  
Giovanni Li Volti ◽  
Carlo Genovese ◽  
...  
Keyword(s):  
Herpes Simplex ◽  
Juglans Regia ◽  
Radical Scavenging ◽  
Fungal Growth ◽  
Bioactive Molecules ◽  
Total Phenolic ◽  
Cytotoxic Activities ◽  
Dependent Manner ◽  
Anion Formation ◽  
Herpes Simplex Viruses

The difficulty to treat resistant strains-related hospital-acquired infections (HAIs) promoted the study of phytoextracts, known sources of bioactive molecules. Accordingly, in the present study, the pharmacological activities of Juglans regia (L.) pellicle extract (WPE) were investigated. The antiviral effect was tested against Herpes simplex virus type 1 and 2, Poliovirus 1, Adenovirus 2, Echovirus 9, Coxsackievirus B1 through the plaque reduction assay. The antibacterial and antifungal activities were evaluated against medically important strains, by the microdilution method. DPPH and superoxide dismutase (SOD)s-like activity assays were used to determine the antioxidant effect. Besides, the extract was screened for cytotoxicity on Caco-2, MCF-7, and HFF1 cell lines by the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay. The total phenolic and flavonoid contents were also evaluated. Interestingly, WPE inhibited Herpes simplex viruses (HSVs) replication, bacterial and fungal growth. WPE showed free radical scavenging capacity and inhibited superoxide anion formation in a dose-dependent manner. These effects could be attributed to the high content of phenols and flavonoids, which were 0.377 ± 0.01 mg GE/g and 0.292 ± 0.08 mg CE/g, respectively. Moreover, WPE was able to reduce Caco-2 cell viability, at both 48 h and 72 h. The promising results encourage further studies aimed to better elucidate the role of WPE in the prevention of human infectious diseases.

Abnormal Spinal Cord Myelination due to Oligodendrocyte Dysfunction in a Model of Huntington’s Disease

2021 ◽  
pp. 1-8
Author(s):  
Costanza Ferrari Bardile ◽  
Harwin Sidik ◽  
Reynard Quek ◽  
Nur Amirah Binte Mohammad Yusof ◽  
Marta Garcia-Miralles ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Oligodendrocyte Progenitor Cells ◽  
Wild Type ◽  
Specific Expression ◽  
Relative Contribution ◽  
Related Proteins ◽  
The Impact ◽  
Cervical Area

Background: The relative contribution of grey matter (GM) and white matter (WM) degeneration to the progressive brain atrophy in Huntington’s disease (HD) has been well studied. The pathology of the spinal cord in HD is comparatively less well documented. Objective: We aim to characterize spinal cord WM abnormalities in a mouse model of HD and evaluate whether selective removal of mutant huntingtin (mHTT) from oligodendroglia rescues these deficits. Methods: Histological assessments were used to determine the area of GM and WM in the spinal cord of 12-month-old BACHD mice, while electron microscopy was used to analyze myelin fibers in the cervical area of the spinal cord. To investigate the impact of inactivation of mHTT in oligodendroglia on these measures, we used the previously described BACHDxNG2Cre mouse line where mHTT is specifically reduced in oligodendrocyte progenitor cells. Results: We show that spinal GM and WM areas are significantly atrophied in HD mice compared to wild-type controls. We further demonstrate that specific reduction of mHTT in oligodendroglial cells rescues the atrophy of spinal cord WM, but not GM, observed in HD mice. Inactivation of mHTT in oligodendroglia had no effect on the density of oligodendroglial cells but enhanced the expression of myelin-related proteins in the spinal cord. Conclusion: Our findings demonstrate that the myelination abnormalities observed in brain WM structures in HD extend to the spinal cord and suggest that specific expression of mHTT in oligodendrocytes contributes to such abnormalities.

Hypoxic stress visualized in the cervical spinal cord of ALS patients

2020 ◽  
pp. 1-5
Author(s):  
Toru Yamashita ◽  
Tetsuhiro Hatakeyama ◽  
Kota Sato ◽  
Yusuke Fukui ◽  
Nozomi Hishikawa ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Cervical Spinal Cord ◽  
Hypoxic Stress ◽  
Als Patients

scholarly journals RBM45 Modulates the Antioxidant Response in Amyotrophic Lateral Sclerosis through Interactions with KEAP1

2015 ◽  
Vol 35 (14) ◽  
pp. 2385-2399 ◽  
Author(s):  
Nadine Bakkar ◽  
Arianna Kousari ◽  
Tina Kovalik ◽  
Yang Li ◽  
Robert Bowser
Keyword(s):  
Oxidative Stress ◽  
Spinal Cord ◽  
Amyotrophic Lateral Sclerosis ◽  
Motor Neurons ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Antioxidant Response ◽  
Cytoplasmic Inclusions ◽  
Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the selective loss of motor neurons. Various factors contribute to the disease, including RNA binding protein dysregulation and oxidative stress, but their exact role in pathogenic mechanisms remains unclear. We have recently linked another RNA binding protein, RBM45, to ALS via increased levels of protein in the cerebrospinal fluid of ALS patients and its localization to cytoplasmic inclusions in ALS motor neurons. Here we show RBM45 nuclear exit in ALS spinal cord motor neurons compared to controls, a phenotype recapitulatedin vitroin motor neurons treated with oxidative stressors. We find that RBM45 binds and stabilizes KEAP1, the inhibitor of the antioxidant response transcription factor NRF2. ALS lumbar spinal cord lysates similarly show increased cytoplasmic binding of KEAP1 and RBM45. Binding of RBM45 to KEAP1 impedes the protective antioxidant response, thus contributing to oxidative stress-induced cellular toxicity. Our findings thus describe a novel link between a mislocalized RNA binding protein implicated in ALS (RBM45) and dysregulation of the neuroprotective antioxidant response seen in the disease.

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