Effect of antioxidants on apoptosis induced by influenza virus infection: inhibition of viral gene replication and transcription with pyrrolidine dithiocarbamate

2002 ◽  
Vol 56 (3) ◽  
pp. 207-217 ◽  
Author(s):  
N UCHIDE ◽  
K OHYAMA ◽  
T BESSHO ◽  
B YUAN ◽  
T YAMAKAWA
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Influenza Virus Infection ◽  
Viral Gene ◽  
Pyrrolidine Dithiocarbamate ◽  
Gene Replication ◽  
Infection Inhibition

Role of oxidants in influenza virus-induced gene expression

1998 ◽  
Vol 274 (1) ◽  
pp. L134-L142 ◽  
Author(s):  
Katharine Knobil ◽  
Augustine M. K. Choi ◽  
Gordon W. Weigand ◽  
David B. Jacoby
Keyword(s):  
Gene Expression ◽  
Cell Death ◽  
Influenza Virus ◽  
Virus Infection ◽  
A549 Cells ◽  
Influenza Virus Infection ◽  
Pyrrolidine Dithiocarbamate ◽  
Oxygen Intermediates ◽  
Mrna Induction

Influenza virus-induced epithelial damage may be mediated, in part, by reactive oxygen intermediates (ROIs). In this study, we investigated the role of ROIs in the influenza virus-induced gene expression of antioxidant enzymes and in the activation of nuclear factor-κB (NF-κB), an oxidant-sensitive transcriptional factor. Influenza virus infection increased production of intracellular ROIs in A549 pulmonary epithelial cells. Induction of manganese superoxide dismutase (MnSOD) mRNA correlated with increased MnSOD protein and enzyme activity. Influenza virus infection also activated NF-κB binding as determined by an electrophoretic mobility shift assay. Pretreatment of A549 cells with N-acetyl-l-cysteine attenuated virus-induced NF-κB activation and interleukin (IL)-8 mRNA induction but did not block induction of MnSOD mRNA. In contrast, pyrrolidine dithiocarbamate blocked activation of NF-κB and induction of MnSOD and IL-8 mRNAs. Treatment with pyrrolidine dithiocarbamate also markedly decreased virus-induced cell death. Thus oxidants are involved in influenza virus-induced activation of NF-κB, in the expression of IL-8 and MnSOD, and in virus-induced cell death.

Therapy of experimental influenza virus infection with pyrrolidine dithiocarbamate

2010 ◽  
Vol 200 (2) ◽  
pp. 115-126 ◽  
Author(s):  
Nadine Wiesener ◽  
Christin Zimmer ◽  
Nadine Jarasch-Althof ◽  
Peter Wutzler ◽  
Andreas Henke
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Influenza Virus Infection ◽  
Pyrrolidine Dithiocarbamate ◽  
Experimental Influenza

scholarly journals Extreme heterogeneity of influenza virus infection in single cells

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Alistair B Russell ◽  
Cole Trapnell ◽  
Jesse D Bloom
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Viral Infection ◽  
Single Cells ◽  
Influenza Virus Infection ◽  
Viral Gene ◽  
Viral Mrnas ◽  
Cellular Genes ◽  
Infected Cells ◽  
Cell Variation

Viral infection can dramatically alter a cell’s transcriptome. However, these changes have mostly been studied by bulk measurements on many cells. Here we use single-cell mRNA sequencing to examine the transcriptional consequences of influenza virus infection. We find extremely wide cell-to-cell variation in the productivity of viral transcription – viral transcripts comprise less than a percent of total mRNA in many infected cells, but a few cells derive over half their mRNA from virus. Some infected cells fail to express at least one viral gene, but this gene absence only partially explains variation in viral transcriptional load. Despite variation in viral load, the relative abundances of viral mRNAs are fairly consistent across infected cells. Activation of innate immune pathways is rare, but some cellular genes co-vary in abundance with the amount of viral mRNA. Overall, our results highlight the complexity of viral infection at the level of single cells.

scholarly journals Influenza Virus NS1 Protein-RNA Interactome Reveals Intron Targeting

2018 ◽  
Vol 92 (24) ◽  
Author(s):  
Liang Zhang ◽  
Juan Wang ◽  
Raquel Muñoz-Moreno ◽  
Min Kim ◽  
Ramanavelan Sakthivel ◽  
...  
Keyword(s):  
Gene Expression ◽  
Influenza Virus ◽  
Virus Infection ◽  
Influenza A ◽  
Rna Binding ◽  
Influenza Virus Infection ◽  
Viral Gene Expression ◽  
Viral Gene ◽  
Ns1 Protein ◽  
Cellular Processes

ABSTRACTThe NS1 protein of influenza A virus is a multifunctional virulence factor that inhibits cellular processes to facilitate viral gene expression. While NS1 is known to interact with RNA and proteins to execute these functions, the cellular RNAs that physically interact with NS1 have not been systematically identified. Here we reveal a NS1 protein-RNA interactome and show that NS1 primarily binds intronic sequences. Among this subset of pre-mRNAs is the RIG-I pre-mRNA, which encodes the main cytoplasmic antiviral sensor of influenza virus infection. This suggested that NS1 interferes with the antiviral response at a posttranscriptional level by virtue of its RNA binding properties. Indeed, we show that NS1 is necessary in the context of viral infection and sufficient upon transfection to decrease the rate of RIG-I intron removal. This NS1 function requires a functional RNA binding domain and is independent of the NS1 interaction with the cleavage and polyadenylation specificity factor CPSF30. NS1 has been previously shown to abrogate RIG-I-mediated antiviral immunity by inhibiting its protein function. Our data further suggest that NS1 also posttranscriptionally alters RIG-I pre-mRNA processing by binding to the RIG-I pre-mRNA.IMPORTANCEA key virulence factor of influenza A virus is the NS1 protein, which inhibits various cellular processes to facilitate viral gene expression. The NS1 protein is localized in the nucleus and in the cytoplasm during infection. In the nucleus, NS1 has functions related to inhibition of gene expression that involve protein-protein and protein-RNA interactions. While several studies have elucidated the protein interactome of NS1, we still lack a clear and systematic understanding of the NS1-RNA interactome. Here we reveal a nuclear NS1-RNA interactome and show that NS1 primarily binds intronic sequences within a subset of pre-mRNAs, including the RIG-I pre-mRNA that encodes the main cytoplasmic antiviral sensor of influenza virus infection. Our data here further suggest that NS1 is necessary and sufficient to impair intron processing of the RIG-I pre-mRNA. These findings support a posttranscriptional role for NS1 in the inhibition of RIG-I expression.

scholarly journals Extreme heterogeneity of influenza virus infection in single cells

2017 ◽  
Author(s):  
Alistair B. Russell ◽  
Cole Trapnell ◽  
Jesse D. Bloom
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Viral Infection ◽  
Single Cells ◽  
Influenza Virus Infection ◽  
Viral Gene ◽  
Viral Mrnas ◽  
Cellular Genes ◽  
Gene Transcripts ◽  
Infected Cells

AbstractViral infection can dramatically alter a cell’s transcriptome. However, these changes have mostly been studied by bulk measurements on many cells. Here we use single-cell mRNA sequencing to examine the transcriptional consequences of Influenza virus infection. We 1nd extremely wide cell-to-cell variation in production of viral gene transcripts – viral transcripts compose less than a percent of total mRNA in many infected cells, but a few cells derive over half their mRNA from virus. Some infected cells fail to express at least one viral gene, and this gene absence partially explains variation in viral transcriptional load. Despite variation in total viral load, the relative abundances of viral mRNAs are fairly consistent across infected cells. Activation of innate immune pathways is rare, but some cellular genes co-vary in abundance with the amount of viral mRNA. Overall, our results highlight the complexity of viral infection at the level of single cells.

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