scholarly journals Two Putative Cypovirus-Encoded miRNAs Co-regulate the Host Gene of GTP-Binding Nuclear Protein Ran and Facilitate Virus Replication

2021 ◽  
Vol 12 ◽  
Author(s):  
Su Lin ◽  
Yongsheng Wang ◽  
Ze Zhao ◽  
Wanming Wu ◽  
Yun Su ◽  
...  
Keyword(s):  
Gene Expression ◽  
Virus Replication ◽  
Target Gene ◽  
Nuclear Protein ◽  
The Body ◽  
Host Gene ◽  
Genomic Rnas ◽  
Gtp Binding ◽  
Effective Multiplication ◽  
Bmn Cells

microRNA (miRNA) plays important roles in regulating various biological processes, including host-pathogen interaction. Recent studies have demonstrated that virus-encoded miRNAs can manipulate host gene expression to ensure viral effective multiplication. Bombyx mori cypovirus (BmCPV), a double-stranded RNA virus with a segmented genome, is one of the important pathogens for the economically important insect silkworm. Our present study indicated that two putative miRNAs encoded by BmCPV could promote viral replication by inhibiting the gene expression of B. mori GTP-binding nuclear protein Ran (BmRan), an essential component of the exportin-5-mediated nucleocytoplasmic transport of small RNAs. BmCPV-miR-1 and BmCPV-miR-3 are two of the BmCPV-encoded miRNAs identified in our previous studies. BmRan is a common target gene of them with binding sites all located in the 3′-untranslated region (3′-UTR) of its mRNA. The expression levels of the two miRNAs in the midgut of larvae infected with BmCPV gradually increased with the advance of infection, while the expression of the target gene BmRan decreased gradually. The miRNAs and the recombinant target gene consisting of reporter gene mCherry and 3′-UTR of BmRan mRNA were expressed in HEK293T cells for validating the interaction between the miRNAs and the target gene. qRT-PCR results revealed that BmCPV-miR-1 and BmCPV-miR-3 negatively regulate target gene expression not only separately but also cooperatively by binding to the 3′-UTR of BmRan mRNA. By transfecting miRNA mimics into BmN cells and injecting the mimics into the body of silkworm larvae, it was indicated that both BmCPV-miR-1 and BmCPV-miR-3 could repress the expression of BmRan in BmN cells and in the silkworm, and the cooperative action of the two miRNAs could enhance the repression of BmRan expression. Furthermore, the repression of BmRan could facilitate the replication of BmCPV genomic RNAs. It is speculated that BmCPV-miR-1 and BmCPV-miR-3 might reduce the generation of host miRNAs by inhibiting expression of BmRan, thus creating a favorable intracellular environment for virus replication. Our results are helpful to better understand the pathogenic mechanism of BmCPV to the silkworm, and provide insights into one of the evasion strategies used by viruses to counter the host defense for their effective multiplication.

scholarly journals Expression of Vitamin D Receptor Pathway Genes in Subcutaneous Adipose Tissue of Obese Individuals

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A658-A658
Author(s):  
Olivia Z B Ginnard ◽  
Stephanie Sisley
Keyword(s):  
Gene Expression ◽  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Subcutaneous Adipose Tissue ◽  
Target Gene ◽  
The Body ◽  
Target Gene Expression ◽  
Vitamin D Levels ◽  
Subcutaneous Adipose ◽  
Gene Expression Levels

Abstract Introduction: Vitamin D deficiency is a substantial comorbidity in 50% of pediatric patients and is linked with poorer health outcomes in children. Vitamin D levels are also shown to be inversely related to BMI. Therefore, there are many more children with low vitamin D levels due to the increasing prevalence of pediatric obesity. Pediatric patients with obesity and vitamin D deficiency also have a uniquely increased risk of metabolic syndrome, as compared to their lean peers. Measured levels of vitamin D correlate with other physiological markers of vitamin D effects in lean individuals but not obese individuals. It is possible that vitamin D levels reflect a storage form of vitamin D rather than a true reflection of vitamin D action in the body in this particular population. The aim of this study was to provide foundational knowledge to understand if expression of vitamin D receptor (VDR)-target genes may be used as a reference standard for vitamin D status in the body. Methods: We performed a secondary analysis of samples obtained from 33 obese adolescents that were consented under a past IRB-approved protocol. They were between the ages of 13 to 18 years that underwent bariatric surgery between 2004 and 2019. Data comprised of age, gender, race/ethnicity, and BMI. Samples collected included blood and subcutaneous adipose tissue. The tissue was analyzed via Real Time-PCR to obtain quantitative levels of VDR-target gene expression, which included PPARg, TLR4, THBD, CYP24A1, and VDR. Gene expression levels were normalized to the average of two housekeeping genes, GAPDH and RPLPO. Blood samples provided vitamin D levels (serum 25(OH)D). Results: VDR-target gene expression was significantly correlated between THBD, VDR, and TLR4 (p <0.05), and PPARg with THBD and TLR4 (p <0.05). There was no correlation observed between CYP24A1 gene expression and the other genes that were evaluated (p >0.05). PPARg, THBD, TLR4, CYP24A1, and VDR gene expression levels did not correlate with circulating serum 25(OH)D levels (p >0.05). Conclusion: These preliminary findings suggest that VDR-target gene expression correlates with each other but not with circulating serum 25(OH)D levels. This discrepancy supports that 25(OH)D levels do not indicate levels of vitamin D action and may not be an appropriate indicator of vitamin D deficiency in the obese population. Also, the observed CYP24A1 gene expression was limited in subcutaneous adipose tissue yet expression was seen in multiple other VDR-target genes. This emphasizes the tissue-specific nature of gene regulation of vitamin D. Further work should investigate VDR-target gene expression levels across multiple tissues of obese individuals to determine if markers of vitamin D action in one tissue are reflective of action across the body. This study may provide the first step in determining a new and more accurate biomarker for vitamin D deficiency and treatment in obesity.

scholarly journals Small Hydrophobic Protein of Human Metapneumovirus Does Not Affect Virus Replication and Host Gene Expression In Vitro

PLoS ONE ◽  
2013 ◽  
Vol 8 (3) ◽  
pp. e58572 ◽  
Author(s):  
Miranda de Graaf ◽  
Sander Herfst ◽  
Jamil Aarbiou ◽  
Peter C. Burgers ◽  
Fatiha Zaaraoui-Boutahar ◽  
...  
Keyword(s):  
Gene Expression ◽  
Virus Replication ◽  
Human Metapneumovirus ◽  
Host Gene ◽  
Host Gene Expression ◽  
Hydrophobic Protein ◽  
Small Hydrophobic Protein ◽  
Small Hydrophobic

scholarly journals The Endonucleolytic RNA Cleavage Function of nsp1 of Middle East Respiratory Syndrome Coronavirus Promotes the Production of Infectious Virus Particles in Specific Human Cell Lines

2018 ◽  
Vol 92 (21) ◽  
Author(s):  
Keisuke Nakagawa ◽  
Krishna Narayanan ◽  
Masami Wada ◽  
Vsevolod L. Popov ◽  
Maria Cajimat ◽  
...  
Keyword(s):  
Gene Expression ◽  
Virus Replication ◽  
Virus Assembly ◽  
Host Gene ◽  
Wild Type Virus ◽  
Rna Cleavage ◽  
Host Gene Expression ◽  
Biological Functions ◽  
Wild Type ◽  
Infected Cells

ABSTRACTMiddle East respiratory syndrome coronavirus (MERS-CoV) nsp1 suppresses host gene expression in expressed cells by inhibiting translation and inducing endonucleolytic cleavage of host mRNAs, the latter of which leads to mRNA decay. We examined the biological functions of nsp1 in infected cells and its role in virus replication by using wild-type MERS-CoV and two mutant viruses with specific mutations in the nsp1; one mutant lacked both biological functions, while the other lacked the RNA cleavage function but retained the translation inhibition function. In Vero cells, all three viruses replicated efficiently with similar replication kinetics, while wild-type virus induced stronger host translational suppression and host mRNA degradation than the mutants, demonstrating that nsp1 suppressed host gene expression in infected cells. The mutant viruses replicated less efficiently than wild-type virus in Huh-7 cells, HeLa-derived cells, and 293-derived cells, the latter two of which stably expressed a viral receptor protein. In 293-derived cells, the three viruses accumulated similar levels of nsp1 and major viral structural proteins and did not induceIFN-β andIFN-λ mRNAs; however, both mutants were unable to generate intracellular virus particles as efficiently as wild-type virus, leading to inefficient production of infectious viruses. These data strongly suggest that the endonucleolytic RNA cleavage function of the nsp1 promoted MERS-CoV assembly and/or budding in a 293-derived cell line. MERS-CoV nsp1 represents the first CoV gene 1 protein that plays an important role in virus assembly/budding and is the first identified viral protein whose RNA cleavage-inducing function promotes virus assembly/budding.IMPORTANCEMERS-CoV represents a high public health threat. Because CoV nsp1 is a major viral virulence factor, uncovering the biological functions of MERS-CoV nsp1 could contribute to our understanding of MERS-CoV pathogenicity and spur development of medical countermeasures. Expressed MERS-CoV nsp1 suppresses host gene expression, but its biological functions for virus replication and effects on host gene expression in infected cells are largely unexplored. We found that nsp1 suppressed host gene expression in infected cells. Our data further demonstrated that nsp1, which was not detected in virus particles, promoted virus assembly or budding in a 293-derived cell line, leading to efficient virus replication. These data suggest that nsp1 plays an important role in MERS-CoV replication and possibly affects virus-induced diseases by promoting virus particle production in infected hosts. Our data, which uncovered an unexpected novel biological function of nsp1 in virus replication, contribute to further understanding of the MERS-CoV replication strategies.

scholarly journals Proteolytic Cleavage of MLL Generates a Complex of N- and C-Terminal Fragments That Confers Protein Stability and Subnuclear Localization

2003 ◽  
Vol 23 (1) ◽  
pp. 186-194 ◽  
Author(s):  
James J.-D. Hsieh ◽  
Patricia Ernst ◽  
Hediye Erdjument-Bromage ◽  
Paul Tempst ◽  
Stanley J. Korsmeyer
Keyword(s):  
Gene Expression ◽  
Target Gene ◽  
Target Genes ◽  
Nuclear Protein ◽  
Marked Decrease ◽  
Stable Complex ◽  
Chimeric Proteins ◽  
Human Leukemia ◽  
Subnuclear Localization ◽  
Chromosome Translocations

ABSTRACT The mixed-lineage leukemia gene (MLL, ALL1, HRX) encodes a 3,969-amino-acid nuclear protein homologous to Drosophila trithorax and is required to maintain proper Hox gene expression. Chromosome translocations in human leukemia disrupt MLL (11q23), generating chimeric proteins between the N terminus of MLL and multiple translocation partners. Here we report that MLL is normally cleaved at two conserved sites (D/GADD and D/GVDD) and that mutation of these sites abolishes the proteolysis. MLL cleavage generates N-terminal p320 (N320) and C-terminal p180 (C180) fragments, which form a stable complex that localizes to a subnuclear compartment. The FYRN domain of N320 directly interacts with the FYRC and SET domains of C180. Disrupting the interaction between N320 and C180 leads to a marked decrease in the level of N320 and a redistribution of C180 to a diffuse nuclear pattern. These data suggest a model in which a dynamic post-cleavage association confers stability to N320 and correct nuclear sublocalization of the complex, to control the availability of N320 for target genes. This predicts that MLL fusion proteins of leukemia which would lose the ability to complex with C180 have their stability conferred instead by the fusion partners, thus providing one mechanism for altered target gene expression.

A comparison between virus replication and abiotic stress (heat) as modifiers of host gene expression in pea

2000 ◽  
Vol 1 (3) ◽  
pp. 159-167 ◽  
Author(s):  
Margarita Escaler ◽  
Miguel A. Aranda ◽  
Ian M. Roberts ◽  
Carole L. Thomas ◽  
Andrew J. Maule
Keyword(s):  
Gene Expression ◽  
Abiotic Stress ◽  
Virus Replication ◽  
Host Gene ◽  
Host Gene Expression

scholarly journals Microbiota prevents cholesterol loss from the body by regulating host gene expression in mice

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Chun-Yan Zhong ◽  
Wei-Wei Sun ◽  
Yinyan Ma ◽  
Hongling Zhu ◽  
Pan Yang ◽  
...  
Keyword(s):  
Gene Expression ◽  
The Body ◽  
Host Gene ◽  
Host Gene Expression

Inhibition of Host Gene Expression Associated with Plant Virus Replication

Science ◽  
1995 ◽  
Vol 267 (5195) ◽  
pp. 229-231 ◽  
Author(s):  
D. Wang ◽  
A. J. Maule
Keyword(s):  
Gene Expression ◽  
Virus Replication ◽  
Plant Virus ◽  
Host Gene ◽  
Host Gene Expression

2049-P: The Chd4 Helicase of the Nucleosome Remodeling and Deacetylase Complex Modulates Pdx1 Target Gene Expression In Vitro

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 2049-P
Author(s):  
REBECCA K. DAVIDSON ◽  
NOLAN CASEY ◽  
JASON SPAETH
Keyword(s):  
Gene Expression ◽  
Target Gene ◽  
Nucleosome Remodeling ◽  
Target Gene Expression

Anti-Diabetic and Angio-Protective Effect of Guluronic Acid (G2013) as a New Nonsteroidal Anti-Inflammatory Drug in the Experimental Model of Diabetes

2020 ◽  
Vol 20 (3) ◽  
pp. 446-452
Author(s):  
Seyed S. Mortazavi-Jahromi ◽  
Shahab Alizadeh ◽  
Mohammad H. Javanbakht ◽  
Abbas Mirshafiey
Keyword(s):  
Gene Expression ◽  
Blood Glucose ◽  
Food Intake ◽  
Experimental Model ◽  
Serum Insulin ◽  
Fasting Blood Glucose ◽  
Diabetic Control ◽  
The Body ◽  
Sprague Dawley ◽  
Guluronic Acid

Background: This study aimed to investigate the effects of guluronic acid (G2013) on blood sugar, insulin, and gene expression profile of oxLDL receptors (SR-A, CD36, LOX-1, and CD68) in the experimental model of diabetes. Methods: 18 Sprague Dawley rats were randomly assigned to three groups of healthy control, diabetic control, and G2013 group. Diabetes was induced through intraperitoneal (IP) injection of 60 mg/kg streptozotocin. The subjects were IP treated with 25 mg/kg of G2013 per day for 28 days. The body weight, food intake, fasting blood glucose and insulin were measured. In addition, the expression of mentioned genes was investigated through quantitative real-time PCR. Results: The data showed that the final weight increased significantly in the G2013-treated subjects compared to the diabetic control (p < 0.05). The results indicated that final food intake significantly reduced in the G2013-treated subjects compared to the diabetic control (p < 0.05). The study findings also suggested that the final fasting blood glucose significantly reduced in the G2013-treated group, whereas the final fasting serum insulin level significantly increased in this group compared to the diabetic control (p < 0.05). Moreover, the gene expression levels of SR-A, CD36, LOX-1, and CD68 in the G2013 group significantly reduced compared to the diabetic control (p < 0.05). Conclusion: This study showed that G2013, could reduce blood glucose and increase insulin levels and reduce the gene expression level of oxLDL receptors. In addition, it may probably play an important role in reducing the severity of diabetes-induced inflammatory symptoms.

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