Application of a recombinant replicase to localize the Trionyx sinensis hemorrhagic syndrome virus and evaluate its effects on antiviral genes of T. sinensis

We previously identified that miR-130a downregulates HCV replication through two independent pathways: restoration of host immune responses and regulation of pyruvate metabolism. In this study, we further sought to explore host antiviral target genes regulated by miR-130a. We performed a RT² Profiler™ PCR array to identify the host antiviral genes regulated by miR-130a. The putative binding sites between miR-130a and its downregulated genes were predicted by miRanda. miR-130a and predicted target genes were over-expressed or knocked down by siRNA or CRISPR/Cas9 gRNA. Selected gene mRNAs and their proteins, together with HCV replication in JFH1 HCV-infected Huh7.5.1 cells were monitored by qRT-PCR and Western blot. We identified 32 genes that were significantly differentially expressed more than 1.5-fold following miR-130a overexpression, 28 of which were upregulated and 4 downregulated. We found that ATG5, a target gene for miR-130a, significantly upregulated HCV replication and downregulated interferon stimulated gene expression. miR-130a downregulated ATG5 expression and its conjugation complex with ATG12. ATG5 and ATG5-ATG12 complex affected interferon stimulated gene (ISG) such as MX1 and OAS3 expression and subsequently HCV replication. We concluded that miR-130a regulates host antiviral response and HCV replication through targeting ATG5 via the ATG5-dependent autophagy pathway.

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Increased expression of intrinsic antiviral genes in HLA-B*57-positive individuals

Journal of Leukocyte Biology ◽

10.1189/jlb.0313150 ◽

2013 ◽

Vol 94 (5) ◽

pp. 1051-1059 ◽

Cited By ~ 12

Author(s):

Rui André Saraiva Raposo ◽

Mohamed Abdel-Mohsen ◽

Sara J. Holditch ◽

Peter J. Kuebler ◽

Rex G. Cheng ◽

...

Keyword(s):

Antiviral Genes

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Suppression of NF-κB Activity: A Viral Immune Evasion Mechanism

Viruses ◽

10.3390/v10080409 ◽

2018 ◽

Vol 10 (8) ◽

pp. 409 ◽

Cited By ~ 20

Author(s):

Liyao Deng ◽

Qiurui Zeng ◽

Mingshu Wang ◽

Anchun Cheng ◽

Renyong Jia ◽

...

Keyword(s):

Immune Evasion ◽

Adaptor Proteins ◽

Nuclear Factor Κb ◽

Deubiquitinating Enzymes ◽

Immune Evasion Mechanism ◽

Viral Immune Evasion ◽

Antiviral Genes ◽

Immunodeficiency Virus ◽

Control And Prevention ◽

Small Hydrophobic

Nuclear factor-κB (NF-κB) is an important transcription factor that induces the expression of antiviral genes and viral genes. NF-κB activation needs the activation of NF-κB upstream molecules, which include receptors, adaptor proteins, NF-κB (IκB) kinases (IKKs), IκBα, and NF-κB dimer p50/p65. To survive, viruses have evolved the capacity to utilize various strategies that inhibit NF-κB activity, including targeting receptors, adaptor proteins, IKKs, IκBα, and p50/p65. To inhibit NF-κB activation, viruses encode several specific NF-κB inhibitors, including NS3/4, 3C and 3C-like proteases, viral deubiquitinating enzymes (DUBs), phosphodegron-like (PDL) motifs, viral protein phosphatase (PPase)-binding proteins, and small hydrophobic (SH) proteins. Finally, we briefly describe the immune evasion mechanism of human immunodeficiency virus 1 (HIV-1) by inhibiting NF-κB activity in productive and latent infections. This paper reviews a viral mechanism of immune evasion that involves the suppression of NF-κB activation to provide new insights into and references for the control and prevention of viral diseases.

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Human cytomegalovirus induces and exploits Roquin to counteract the IRF1-mediated antiviral state

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1909314116 ◽

2019 ◽

Vol 116 (37) ◽

pp. 18619-18628 ◽

Cited By ~ 2

Author(s):

Jaewon Song ◽

Sanghyun Lee ◽

Dong-Yeon Cho ◽

Sungwon Lee ◽

Hyewon Kim ◽

...

Keyword(s):

Human Cytomegalovirus ◽

Rna Processing ◽

Rna Binding ◽

Binding Protein ◽

Rna Binding Protein ◽

Transcriptome Profiling ◽

Loss Of Function ◽

Antiviral Genes ◽

Cellular Antiviral Response ◽

Infected Cells

RNA represents a pivotal component of host–pathogen interactions. Human cytomegalovirus (HCMV) infection causes extensive alteration in host RNA metabolism, but the functional relationship between the virus and cellular RNA processing remains largely unknown. Through loss-of-function screening, we show that HCMV requires multiple RNA-processing machineries for efficient viral lytic production. In particular, the cellular RNA-binding protein Roquin, whose expression is actively stimulated by HCMV, plays an essential role in inhibiting the innate immune response. Transcriptome profiling revealed Roquin-dependent global down-regulation of proinflammatory cytokines and antiviral genes in HCMV-infected cells. Furthermore, using cross-linking immunoprecipitation (CLIP)-sequencing (seq), we identified IFN regulatory factor 1 (IRF1), a master transcriptional activator of immune responses, as a Roquin target gene. Roquin reduces IRF1 expression by directly binding to its mRNA, thereby enabling suppression of a variety of antiviral genes. This study demonstrates how HCMV exploits host RNA-binding protein to prevent a cellular antiviral response and offers mechanistic insight into the potential development of CMV therapeutics.

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Epigenetic Silencing of Antiviral Genes Renders Clones of Huh-7 Cells Permissive for Hepatitis C Virus Replication

Journal of Virology ◽

10.1128/jvi.01984-12 ◽

2012 ◽

Vol 87 (1) ◽

pp. 659-665 ◽

Cited By ~ 11

Author(s):

Q. Chen ◽

B. Denard ◽

H. Huang ◽

J. Ye

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Virus Replication ◽

Epigenetic Silencing ◽

Antiviral Genes

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Lipopolysaccharide Stimulates p38-dependent Induction of Antiviral Genes in Neutrophils Independently of Paracrine Factors

Journal of Biological Chemistry ◽

10.1074/jbc.m212033200 ◽

2003 ◽

Vol 278 (18) ◽

pp. 15693-15701 ◽

Cited By ~ 31

Author(s):

Kenneth C. Malcolm ◽

G. Scott Worthen

Keyword(s):

Paracrine Factors ◽

Antiviral Genes

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Interferon-Induced Protein 44 and Interferon-Induced Protein 44-Like Restrict Replication of Respiratory Syncytial Virus

Journal of Virology ◽

10.1128/jvi.00297-20 ◽

2020 ◽

Vol 94 (18) ◽

Cited By ~ 2

Author(s):

D. C. Busse ◽

D. Habgood-Coote ◽

S. Clare ◽

C. Brandt ◽

I. Bassano ◽

...

Keyword(s):

Respiratory Syncytial Virus ◽

Mouse Model ◽

Severe Disease ◽

Early Time ◽

Airway Epithelial Cells ◽

Knockout Mouse Model ◽

Antiviral Genes ◽

Wide Range ◽

Rsv Infection ◽

Syncytial Virus

ABSTRACT Cellular intrinsic immunity, mediated by the expression of an array of interferon-stimulated antiviral genes, is a vital part of host defense. We have previously used a bioinformatic screen to identify two interferon-stimulated genes (ISG) with poorly characterized function, interferon-induced protein 44 (IFI44) and interferon-induced protein 44-like (IFI44L), as potentially being important in respiratory syncytial virus (RSV) infection. Using overexpression systems, CRISPR-Cas9-mediated knockout, and a knockout mouse model, we investigated the antiviral capability of these genes in the control of RSV replication. Overexpression of IFI44 or IFI44L was sufficient to restrict RSV infection at an early time postinfection. Knocking out these genes in mammalian airway epithelial cells increased levels of infection. Both genes express antiproliferative factors that have no effect on RSV attachment but reduce RSV replication in a minigenome assay. The loss of Ifi44 was associated with a more severe infection phenotype in a mouse model of infection. These studies demonstrate a function for IFI44 and IFI44L in controlling RSV infection. IMPORTANCE RSV infects all children under 2 years of age, but only a subset of children get severe disease. We hypothesize that susceptibility to severe RSV necessitating hospitalization in children without predefined risk factors is, in part, mediated at the antiviral gene level. However, there is a large array of antiviral genes, particularly in the ISG family, the mechanism of which is poorly understood. Having previously identified IFI44 and IFI44L as possible genes of interest in a bioinformatic screen, we dissected the function of these two genes in the control of RSV. Through a range of overexpression and knockout studies, we show that the genes are antiviral and antiproliferative. This study is important because IFI44 and IFI44L are upregulated after a wide range of viral infections, and IFI44L can serve as a diagnostic biomarker of viral infection.

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Analysis of the Early Immune Response to Infection by Infectious Bursal Disease Virus in Chickens Differing in Their Resistance to the Disease

Journal of Virology ◽

10.1128/jvi.02828-14 ◽

2014 ◽

Vol 89 (5) ◽

pp. 2469-2482 ◽

Cited By ~ 27

Author(s):

Jacqueline Smith ◽

Jean-Remy Sadeyen ◽

Colin Butter ◽

Pete Kaiser ◽

David W. Burt

Keyword(s):

Gene Expression ◽

Disease Virus ◽

Infectious Bursal Disease Virus ◽

Host Response ◽

Infectious Bursal Disease ◽

Expression Arrays ◽

Gene Expression Arrays ◽

Antiviral Genes ◽

Bursal Disease ◽

Comprehensive Study

ABSTRACTChicken whole-genome gene expression arrays were used to analyze the host response to infection by infectious bursal disease virus (IBDV). Spleen and bursal tissue were examined from control and infected birds at 2, 3, and 4 days postinfection from two lines that differ in their resistance to IBDV infection. The host response was evaluated over this period, and differences between susceptible and resistant chicken lines were examined. Antiviral genes, includingIFNA,IFNG,MX1,IFITM1,IFITM3, andIFITM5, were upregulated in response to infection. Evaluation of this gene expression data allowed us to predict several genes as candidates for involvement in resistance to IBDV.IMPORTANCEInfectious bursal disease (IBD) is of economic importance to the poultry industry and thus is also important for food security. Vaccines are available, but field strains of the virus are of increasing virulence. There is thus an urgent need to explore new control solutions, one of which would be to breed birds with greater resistance to IBD. This goal is perhaps uniquely achievable with poultry, of all farm animal species, since the genetics of 85% of the 60 billion chickens produced worldwide each year is under the control of essentially two breeding companies. In a comprehensive study, we attempt here to identify global transcriptomic differences in the target organ of the virus between chicken lines that differ in resistance and to predict candidate resistance genes.

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