Critical roles of chemokines and cytokines in antiviral innate immune responses during rabies virus infection

Huang, Ying; Gnanadurai, Clement W.; Fu, Zhenfang

doi:10.15302/j-fase-2016116

Cited by 5 publications

(3 citation statements)

References 64 publications

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“…We also noticed that 6(OH)Mel can enhance the C-X-C motif chemokine ligand 1 (CXCL1) level ( Figure 4 D). CXCL1 is an antimicrobial protein, which also plays a role in the antiviral innate immune response [ 62 ]. These findings are consistent with the above bioinformatic analyses and well-documented immunomodulatory and protective properties of melatonin [ 63 ].…”

Section: Resultsmentioning

confidence: 99%

Differential and Overlapping Effects of Melatonin and Its Metabolites on Keratinocyte Function: Bioinformatics and Metabolic Analyses

et al. 2021

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We investigated the effects of melatonin and its selected metabolites, i.e., N1-Acetyl-N2-formyl-5-methoxykynurenamine (AFMK) and 6-hydroxymelatonin (6(OH)Mel), on cultured human epidermal keratinocytes (HEKs) to assess their homeostatic activities with potential therapeutic implications. RNAseq analysis revealed a significant number of genes with distinct and overlapping patterns, resulting in common regulation of top diseases and disorders. Gene Set Enrichment Analysis (GSEA), Reactome FIViZ, and Ingenuity Pathway Analysis (IPA) showed overrepresentation of the p53-dependent G1 DNA damage response gene set, activation of p53 signaling, and NRF2-mediated antioxidative pathways. Additionally, GSEA exhibited an overrepresentation of circadian clock and antiaging signaling gene sets by melatonin derivatives and upregulation of extension of telomere signaling in HEKs, which was subsequently confirmed by increased telomerase activity in keratinocytes, indicating possible antiaging properties of metabolites of melatonin. Furthermore, Gene Ontology (GO) showed the activation of a keratinocyte differentiation program by melatonin, and GSEA indicated antitumor and antilipidemic potential of melatonin and its metabolites. IPA also indicated the role of Protein Kinase R (PKR) in interferon induction and antiviral response. In addition, the test compounds decreased lactate dehydrogenase A (LDHA) and lactate dehydrogenase C (LDHC) gene expression. These results were validated by qPCR and by Seahorse metabolic assay with significantly decreased glycolysis and lactate production under influence of AFMK or 6(OH)Mel in cells with a low oxygen consumption rate. In summary, melatonin and its metabolites affect keratinocytes’ functions via signaling pathways that overlap for each tested molecule with some distinctions.

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Section: Resultsmentioning

confidence: 99%

Differential and Overlapping Effects of Melatonin and Its Metabolites on Keratinocyte Function: Bioinformatics and Metabolic Analyses

et al. 2021

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“…Rabies virus (RABV) genomes contain five genes, each of which encodes multi-functional proteins with the ability to affect the host immune response in some way to aid the replication and spread of the virus [ 18 ]. The importance of these immune-suppressive effects is evident when comparing laboratory-attenuated strains to wild-type RABVs, as the former lack many of these immune-suppressive capabilities, enabling the virus to be cleared from the central nervous system (CNS) by the host’s immune response [ 19 ]. Furthermore, studies have demonstrated that it is feasible to clear wild-type RABV infection from the CNS when the host immune response remains unimpeded [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

Rabies Prophylactic and Treatment Options: An In Vitro Study of siRNA- and Aptamer-Based Therapeutics

Scott

Nel

2021

Viruses

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If the goal of eliminating dog-mediated human rabies by 2030 is to be achieved, effective mass dog vaccination needs to be complemented by effective prophylaxis for individuals exposed to rabies. Aptamers and short-interfering RNAs (siRNAs) have been successful in therapeutics, but few studies have investigated their potential as rabies therapeutics. In this study, siRNAs and aptamers—using a novel selection method—were developed and tested against rabies virus (RABV) in a post-infection (p.i.) scenario. Multiple means of delivery were tested for siRNAs, including the use of Lipofectamine and conjugation with the developed aptamers. One siRNA (N53) resulted in an 80.13% reduction in viral RNA, while aptamer UPRET 2.03 demonstrated a 61.3% reduction when used alone at 2 h p.i. At 24 h p.i., chimera UPRET 2.03-N8 (aptamer-siRNA) resulted in a 36.5% inhibition of viral replication. To our knowledge, this is the first study using siRNAs or aptamers that (1) demonstrated significant inhibition of RABV using an aptamer, (2) tested Lipofectamine RNAi-Max as a means for delivery, and (3) produced significant RABV inhibition at 24 h p.i. This study serves as a proof-of-concept to potentially use aptamers and siRNAs as rabies immunoglobulin (RIG) replacements or therapeutic options for RABV and provides strong evidence towards their further investigation.

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“…Cytokines are mainly proteins or peptides generally associated with inflammation and cell differentiation, including interleukins (IL), interferons (IFNs), etc. They can contribute to the diagnosis and treatment of diseases [ 1 , 2 ], for example, they are conducive to the treatment of hematopoietic dysfunction [ 3 ], tumor [ 4 ], infection [ 5 , 6 ] and inflammation [ 7 , 8 ]. With the post-genomic era coming, the quantity of new proteins has increased dramatically.…”

Section: Introductionmentioning

confidence: 99%

A New Method for Recognizing Cytokines Based on Feature Combination and a Support Vector Machine Classifier

et al. 2018

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Research on cytokine recognition is of great significance in the medical field due to the fact cytokines benefit the diagnosis and treatment of diseases, but the current methods for cytokine recognition have many shortcomings, such as low sensitivity and low F-score. Therefore, this paper proposes a new method on the basis of feature combination. The features are extracted from compositions of amino acids, physicochemical properties, secondary structures, and evolutionary information. The classifier used in this paper is SVM. Experiments show that our method is better than other methods in terms of accuracy, sensitivity, specificity, F-score and Matthew’s correlation coefficient.

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Critical roles of chemokines and cytokines in antiviral innate immune responses during rabies virus infection

Cited by 5 publications

References 64 publications

Differential and Overlapping Effects of Melatonin and Its Metabolites on Keratinocyte Function: Bioinformatics and Metabolic Analyses

Differential and Overlapping Effects of Melatonin and Its Metabolites on Keratinocyte Function: Bioinformatics and Metabolic Analyses

Rabies Prophylactic and Treatment Options: An In Vitro Study of siRNA- and Aptamer-Based Therapeutics

A New Method for Recognizing Cytokines Based on Feature Combination and a Support Vector Machine Classifier

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