scholarly journals Comprehensive Transcriptomic Analysis Identifies Novel Antiviral Factors Against Influenza A Virus Infection

2021 ◽  
Vol 12 ◽  
Author(s):  
Ao Zhou ◽  
Xia Dong ◽  
Mengyun Liu ◽  
Bin Tang
Keyword(s):  
Epithelial Cells ◽  
Virus Infection ◽  
Influenza A Virus ◽  
Broad Spectrum ◽  
Influenza A ◽  
Cell Types ◽  
Immune Defense ◽  
Host Responses ◽  
Different Cell Types ◽  
Host Genes

Influenza A virus (IAV) has a higher genetic variation, leading to the poor efficiency of traditional vaccine and antiviral strategies targeting viral proteins. Therefore, developing broad-spectrum antiviral treatments is particularly important. Host responses to IAV infection provide a promising approach to identify antiviral factors involved in virus infection as potential molecular drug targets. In this study, in order to better illustrate the molecular mechanism of host responses to IAV and develop broad-spectrum antiviral drugs, we systematically analyzed mRNA expression profiles of host genes in a variety of human cells, including transformed and primary epithelial cells infected with different subtypes of IAV by mining 35 microarray datasets from the GEO database. The transcriptomic results showed that IAV infection resulted in the difference in expression of amounts of host genes in all cell types, especially those genes participating in immune defense and antiviral response. In addition, following the criteria of P<0.05 and |logFC|≥1.5, we found that some difference expression genes were overlapped in different cell types under IAV infection via integrative gene network analysis. IFI6, IFIT2, ISG15, HERC5, RSAD2, GBP1, IFIT3, IFITM1, LAMP3, USP18, and CXCL10 might act as key antiviral factors in alveolar basal epithelial cells against IAV infection, while BATF2, CXCL10, IFI44L, IL6, and OAS2 played important roles in airway epithelial cells in response to different subtypes of IAV infection. Additionally, we also revealed that some overlaps (BATF2, IFI44L, IFI44, HERC5, CXCL10, OAS2, IFIT3, USP18, OAS1, IFIT2) were commonly upregulated in human primary epithelial cells infected with high or low pathogenicity IAV. Moreover, there were similar defense responses activated by IAV infection, including the interferon-regulated signaling pathway in different phagocyte types, although the differentially expressed genes in different phagocyte types showed a great difference. Taken together, our findings will help better understand the fundamental patterns of molecular responses induced by highly or lowly pathogenic IAV, and the overlapped genes upregulated by IAV in different cell types may act as early detection markers or broad-spectrum antiviral targets.

scholarly journals Influenza A Virus Infection Induces Apical Redistribution of Na+, K+-ATPase in Lung Epithelial Cells In Vitro and In Vivo

2019 ◽  
Vol 61 (3) ◽  
pp. 395-398
Author(s):  
Christin Peteranderl ◽  
Irina Kuznetsova ◽  
Jessica Schulze ◽  
Martin Hardt ◽  
Emilia Lecuona ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Virus Infection ◽  
Influenza A Virus ◽  
Influenza A ◽  
Lung Epithelial Cells ◽  
Lung Epithelial ◽  
Influenza A Virus Infection

scholarly journals Ciliostasis of airway epithelial cells facilitates influenza A virus infection

2018 ◽  
Vol 49 (1) ◽  
Author(s):  
Yuguang Fu ◽  
Jie Tong ◽  
Fandan Meng ◽  
Doris Hoeltig ◽  
Guangliang Liu ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Virus Infection ◽  
Influenza A Virus ◽  
Influenza A ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Influenza A Virus Infection

scholarly journals Glycan Analysis and Influenza A Virus Infection of Primary Swine Respiratory Epithelial Cells

2010 ◽  
Vol 285 (44) ◽  
pp. 34016-34026 ◽  
Author(s):  
Allen C. Bateman ◽  
Rositsa Karamanska ◽  
Marc G. Busch ◽  
Anne Dell ◽  
Christopher W. Olsen ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Virus Infection ◽  
Influenza A Virus ◽  
Influenza A ◽  
Respiratory Epithelial Cells ◽  
Glycan Analysis ◽  
Influenza A Virus Infection ◽  
Respiratory Epithelial

scholarly journals Itaconate and derivatives reduce interferon responses and inflammation in influenza A virus infection

2021 ◽  
Author(s):  
Aaqib Sohail ◽  
Azeem A. Iqbal ◽  
Nishika Sahini ◽  
Mohamed Tantawy ◽  
Moritz Winterhoff ◽  
...  
Keyword(s):  
Virus Infection ◽  
Viral Replication ◽  
Influenza A Virus ◽  
Influenza A ◽  
Pulmonary Inflammation ◽  
Transcriptome Profiling ◽  
Host Responses ◽  
Monocytes And Macrophages ◽  
Influenza A Virus Infection ◽  
Interferon Responses

AbstractItaconate has recently emerged as a metabolite with immunomodulatory properties. We evaluated effects of endogenous itaconate and exogenous itaconate, dimethyl-, and 4-octyl-itaconate on host responses to influenza A virus infection. Infection induced ACOD1 (the enzyme catalyzing itaconate synthesis) mRNA in monocytes and macrophages, which correlated with viral replication and was abrogated by itaconate treatment. Pulmonary inflammation and weight loss were greater in Acod1-/- than wild-type mice, and ectopic synthesis of itaconate in human epithelial cells reduced infection-induced inflammation. The compounds induced different recruitment programs in infected human macrophages, and transcriptome profiling revealed that they reversed infection-triggered interferon responses and modulated inflammation in cell lines, PBMC, and lung tissue. Single-cell RNA sequencing of PBMC revealed that infection induced ACOD1 exclusively in monocytes, whereas treatment silenced IFN-responses in monocytes, lymphocytes, and NK cells. Viral replication did not increase under treatment despite the dramatically repressed IFN responses, but 4-octyl itaconate inhibited viral transcription in PBMC. The results reveal dramatic reprogramming of host responses by itaconate and derivatives and their potential as adjunct treatments for hyperinflammation in viral infection.

scholarly journals Unique Transcriptional Architecture in Airway Epithelial Cells and Macrophages Shapes Distinct Responses following Influenza Virus Infection Ex Vivo

2019 ◽  
Vol 93 (6) ◽  
Author(s):  
Joel Z. Ma ◽  
Wy Ching Ng ◽  
Luke Zappia ◽  
Linden J. Gearing ◽  
Moshe Olshansky ◽  
...  
Keyword(s):  
Steady State ◽  
Epithelial Cells ◽  
Rna Sequencing ◽  
Influenza A Virus ◽  
Influenza A ◽  
Cell Types ◽  
Airway Epithelial Cells ◽  
Type I ◽  
Airway Epithelial ◽  
Transcriptional Responses

ABSTRACT Airway epithelial cells and macrophages differ markedly in their responses to influenza A virus (IAV) infection. To investigate transcriptional responses underlying these differences, purified subsets of type II airway epithelial cells (ATII) and alveolar macrophages (AM) recovered from the lungs of mock- or IAV-infected mice at 9 h postinfection were subjected to RNA sequencing. This time point was chosen to allow for characterization of cell types first infected with the virus inoculum, prior to multicycle virus replication and the infiltration of inflammatory cells into the airways. In the absence of infection, AM predominantly expressed genes related to immunity, whereas ATII expressed genes consistent with their physiological roles in the lung. Following IAV infection, AM almost exclusively activated cell-intrinsic antiviral pathways that were dependent on interferon (IFN) regulatory factor 3/7 (IRF3/7) and/or type I IFN signaling. In contrast, IAV-infected ATII activated a broader range of physiological responses, including cell-intrinsic antiviral pathways, which were both independent of and dependent on IRF3/7 and/or type I IFN. These data suggest that transcriptional profiles hardwired during development are a major determinant underlying the different responses of ATII and AM to IAV infection. IMPORTANCE Airway epithelial cells (AEC) and airway macrophages (AM) represent major targets of influenza A virus (IAV) infection in the lung, yet the two cell types respond very differently to IAV infection. We have used RNA sequencing to define the host transcriptional responses in each cell type under steady-state conditions as well as following IAV infection. To do this, different cell subsets isolated from the lungs of mock- and IAV-infected mice were subjected to RNA sequencing. Under steady-state conditions, AM and AEC express distinct transcriptional activities, consistent with distinct physiological roles in the airways. Not surprisingly, these cells also exhibited major differences in transcriptional responses following IAV infection. These studies shed light on how the different transcriptional architectures of airway cells from two different lineages drive transcriptional responses to IAV infection.

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