Distinct antiviral signatures revealed by the magnitude and round of influenza virus replication in vivo

Sjaastad, Louisa E.; Fay, Elizabeth J.; Fiege, Jessica K.; Macchietto, Marissa; Stone, Ian A.; Markman, Matthew W.; Shen, Steven S.; Langlois, Ryan A.

doi:10.1073/pnas.1807516115

Cited by 38 publications

(31 citation statements)

References 50 publications

(58 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…One or combinations of these proposed mechanisms could contribute to the heterogeneity of IFN responses observed within IAV-infected lungs. Additionally, the viral burden among cells has recently been shown to be associated with the expression of different clusters of anti-viral responses (Sjaastad et al, 2018), suggesting that there may be a cell-type-specific switch that regulates antiviral gene expression depending on severity of infection.…”

Section: Discussionmentioning

confidence: 99%

Visualizing the Selectivity and Dynamics of Interferon Signaling In Vivo

et al. 2019

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

Visualizing the Selectivity and Dynamics of Interferon Signaling In Vivo

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Several recent studies have used different approaches to gain insight regarding the transcriptional responses in airway cells in response to influenza virus infection. Elegant experiments using single-cycle reporter viruses and mRNA-seq in CD45 Ϫ CD31 Ϫ "bulk" AEC isolated from IAV-infected mice revealed that uninfected AEC as well as AEC with low and high levels of virus replication all expressed unique IFN-stimulated gene (ISG) signatures (19). Studies reported by Hancock et al focused on transcriptional responses in bulk ATII, but not other cell types, that were directly infected (defined by expression of green fluorescent protein [GFP]) or bystander cells isolated from mice 3 days after infection with PR8 or from uninfected mice (20).…”

Section: Discussionmentioning

confidence: 99%

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

Joel

Zappia

et al. 2019

J Virol

View full text Add to dashboard Cite

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.

show abstract

“…In recent years, many studies in the field have used next generation sequencing technology to assess host cell gene expression profiles, which have led to better understandings of the virus-host cell interaction processes in vitro or in vivo. These studies have provided profound insights into host cell gene expression patterns and antiviral interferon-stimulated gene (ISG) dynamics during infection (Schoggins, 2014;Sjaastad et al, 2018). Most these studies only focused on gene expression profiling and left the activity of transposable elements (TEs) unexplored.…”

Section: Introductionmentioning

confidence: 99%

Virus-induced transposable element expression up-regulation in human and mouse host cells

2020

View full text Add to dashboard Cite

Virus–host cell interactions initiate a host cell–defensive response during virus infection. How transposable elements in the host cell respond to viral stress at the molecular level remains largely unclear. By reanalyzing next generation sequencing data sets from dozens of virus infection studies from the Gene Expression Omnibus database, we found that genome-wide transposon expression up-regulation in host cells occurs near antiviral response genes and exists in all studies regardless of virus, species, and host cell tissue types. Some transposons were found to be up-regulated almost immediately upon infection and before increases in virus replication and significant increases in interferon β expression. These findings indicate that transposon up-regulation is a common phenomenon during virus infection in human and mouse and that early up-regulated transposons are part of the first wave response during virus infection.

show abstract

Distinct antiviral signatures revealed by the magnitude and round of influenza virus replication in vivo

Cited by 38 publications

References 50 publications

Visualizing the Selectivity and Dynamics of Interferon Signaling In Vivo

Visualizing the Selectivity and Dynamics of Interferon Signaling In Vivo

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

Virus-induced transposable element expression up-regulation in human and mouse host cells

Contact Info

Product

Resources

About