Regulation of Early Host Immune Responses Shapes the Pathogenicity of Avian Influenza A Virus

Sun, Jiya; Wang, Jingfeng; Yuan, Xuye; Wu, Xiangwei; Sui, Tianqi; Wu, Aiping; Cheng, Genhong; Jiang, Taijiao

doi:10.3389/fmicb.2019.02007

Cited by 10 publications

(9 citation statements)

References 60 publications

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“…Generally, once the virus enters the cell, the host innate immune responses, such as the interferon-mediated antiviral responses and cytokine production, play a pivotal role in suppressing the virus replication, which, if inadequate, might contribute to the viral pathogenesis. This hypothesis has been supported by our previous study, which has shown that the high pathogenicity of avian influenza virus is associated with abnormal coordination between interferon-mediated antiviral responses and cytokine production in host cells ( Sun et al, 2019 ). Similar to both SARS-CoV and MERS-CoV, which induce the overactivation of cytokines ( Channappanavar and Perlman, 2017 ; Song et al, 2019 ), increased cytokine levels are also observed in patients hospitalized with COVID-19 ( Huang et al, 2020 ).…”

Section: Introductionsupporting

confidence: 61%

“…To quantify host antiviral capacity and inflammation responses during infection of the three viruses, two sets of genes were used as their indicators. First, we used a set of 45 early induced genes in interferon-α treated Calu-3 cell ( Sun et al, 2019 ) as antiviral indicators to quantify the level of host antiviral capacity against SARS-CoV-2, SARS-CoV, and MERS-CoV infections. Our analysis showed that the antiviral capacity of the host against SARS-CoV-2 was gradually increased over the time course of infection ( Figure 3A ).…”

Section: Resultsmentioning

confidence: 99%

“…GO term relationships were extracted from the “go-basic.obo” file 2 . For analysis of microarray data of SARS-CoV and MERS-CoV, normalization and identification of DEGs (FDR < 0.05, | log2FC| ≥ 1) were conducted using the R package limma ( Ritchie et al, 2015 ) by following the steps in our previous study ( Sun et al, 2019 ).…”

Section: Methodsmentioning

confidence: 99%

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Comparative Transcriptome Analysis Reveals the Intensive Early Stage Responses of Host Cells to SARS-CoV-2 Infection

Sun

et al. 2020

Front. Microbiol.

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a widespread outbreak of highly pathogenic coronavirus disease 2019 (COVID-19). It is therefore important and timely to characterize interactions between the virus and host cell at the molecular level to understand its disease pathogenesis. To gain insights, we performed high-throughput sequencing that generated time-series data simultaneously for bioinformatics analysis of virus genomes and host transcriptomes implicated in SARS-CoV-2 infection. Our analysis results showed that the rapid growth of the virus was accompanied by an early intensive response of host genes. We also systematically compared the molecular footprints of the host cells in response to SARS-CoV-2, SARS-CoV, and Middle East respiratory syndrome coronavirus (MERS-CoV). Upon infection, SARS-CoV-2 induced hundreds of up-regulated host genes hallmarked by a significant cytokine production, followed by virus-specific host antiviral responses. While the cytokine and antiviral responses triggered by SARS-CoV and MERS-CoV were only observed during the late stage of infection, the host antiviral responses during the SARS-CoV-2 infection were gradually enhanced lagging behind the production of cytokine. The early rapid host responses were potentially attributed to the high efficiency of SARS-CoV-2 entry into host cells, underscored by evidence of a remarkably up-regulated gene expression of TPRMSS2 soon after infection. Taken together, our findings provide novel molecular insights into the mechanisms underlying the infectivity and pathogenicity of SARS-CoV-2.

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Section: Introductionsupporting

confidence: 61%

Section: Resultsmentioning

confidence: 99%

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Comparative Transcriptome Analysis Reveals the Intensive Early Stage Responses of Host Cells to SARS-CoV-2 Infection

Sun

et al. 2020

Front. Microbiol.

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“…Generally, once the virus enters the cell, the host innate immune responses, such as the interferon-mediated antiviral responses and cytokine production, have a pivotal role in suppressing the virus replication, which, if inadequate, might contribute to the viral pathogenesis. This hypothesis has been supported by our previous study, which has shown that the high pathogenicity of avian influenza virus is associated with abnormal coordination between interferon-mediated antiviral responses and cytokine production in host cells [7]. Similar to both SARS-CoV and MERS-CoV, which induce the overactivation of cytokines [8], increased cytokine levels are also observed in patients hospitalized with COVID-19 [9].…”

Section: Introductionsupporting

confidence: 53%

Comparative transcriptome analysis reveals the intensive early-stage responses of host cells to SARS-CoV-2 infection

Sun

et al. 2020

Preprint

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a widespread outbreak of highly pathogenic COVID-19. It is therefore important and timely to characterize interactions between the virus and host cell at the molecular level to understand its disease pathogenesis. To gain insights, we performed high-throughput sequencing that generated time-series data simultaneously for bioinformatics analysis of virus genomes and host transcriptomes implicated in SARS-CoV-2 infection. Our analysis results showed that the rapid growth of the virus was accompanied by an early intensive response of host genes. We also systematically compared the molecular footprints of the host cells in response to SARS-CoV-2, SARS-CoV and MERS-CoV. Upon infection, SARS-CoV-2 induced hundreds of up-regulated host genes hallmarked by a significant cytokine production followed by virus-specific host antiviral responses. While the cytokine and antiviral responses triggered by SARS-CoV and MERS-CoV were only observed during the late stage of infection, the host antiviral responses during the SARS-CoV-2 infection were gradually enhanced lagging behind the production of cytokine. The early rapid host responses were potentially attributed to the high efficiency of SARS-CoV-2 entry into host cells, underscored by evidence of a remarkably up-regulated gene expression of TPRMSS2 soon after infection. Taken together, our findings provide novel molecular insights into the mechanisms underlying the infectivity and pathogenicity of SARS-CoV-2.

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“…On the other hand, virus infections trigger the production of inflammatory cytokines and chemokines in the respiratory tract including interleukin (IL)-6, chemokine (C-C motif) ligand 2 (CCL2), CCL5, CCL8, chemokine (C-X-C motif) ligand 8 (CXCL8), CXCL9, CXCL16, and CXCL2. While these inflammatory factors play a pivotal role in suppressing virus replication by recruiting and activating immune cells, the inadequate production of inflammatory factors might contribute to the viral pathogenesis [ 12 ]. Thus, the severity of COVID-19 depends not only on the SARS-CoV-2-induced cellular injury, but also on the host immune response [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Immunobiotic Lactobacilli Improve Resistance of Respiratory Epithelial Cells to SARS-CoV-2 Infection

et al. 2021

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Previously, we reported that immunomodulatory lactobacilli, nasally administered, beneficially regulated the lung antiviral innate immune response induced by Toll-like receptor 3 (TLR3) activation and improved protection against the respiratory pathogens, influenza virus and respiratory syncytial virus in mice. Here, we assessed the immunomodulatory effects of viable and non-viable Lactiplantibacillus plantarum strains in human respiratory epithelial cells (Calu-3 cells) and the capacity of these immunobiotic lactobacilli to reduce their susceptibility to the acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Immunobiotic L. plantarum MPL16 and CRL1506 differentially modulated IFN-β, IL-6, CXCL8, CCL5 and CXCL10 production and IFNAR2, DDX58, Mx1 and OAS1 expression in Calu-3 cells stimulated with the TLR3 agonist poly(I:C). Furthermore, the MPL16 and CRL1506 strains increased the resistance of Calu-3 cells to the challenge with SARS-CoV-2. L. plantarum MPL16 induced these beneficial effects more efficiently than the CRL1506 strain. Of note, neither non-viable MPL16 and CRL1506 strains nor the non-immunomodulatory strains L. plantarum CRL1905 and MPL18 could modify the resistance of Calu-3 cells to SARS-CoV-2 infection or the immune response to poly(I:C) challenge. To date, the potential beneficial effects of immunomodulatory probiotics on SARS-CoV-2 infection and COVID-19 outcome have been extrapolated from studies carried out in the context of other viral pathogens. To the best of our knowledge, this is the first demonstration of the ability of immunomodulatory lactobacilli to positively influence the replication of the new coronavirus. Further mechanistic studies and in vivo experiments in animal models of SARS-CoV-2 infection are necessary to identify specific strains of beneficial immunobiotic lactobacilli like L. plantarum MPL16 or CRL1506 for the prevention or treatment of the COVID-19.

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Regulation of Early Host Immune Responses Shapes the Pathogenicity of Avian Influenza A Virus

Cited by 10 publications

References 60 publications

Comparative Transcriptome Analysis Reveals the Intensive Early Stage Responses of Host Cells to SARS-CoV-2 Infection

Comparative Transcriptome Analysis Reveals the Intensive Early Stage Responses of Host Cells to SARS-CoV-2 Infection

Comparative transcriptome analysis reveals the intensive early-stage responses of host cells to SARS-CoV-2 infection

Immunobiotic Lactobacilli Improve Resistance of Respiratory Epithelial Cells to SARS-CoV-2 Infection

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