Severe Infection With Avian Influenza A Virus is Associated With Delayed Immune Recovery in Survivors

Chen, Jianing; Cui, Guangying; Lu, Chong; Ding, Yuhao; Gao, Hainv; Zhu, Yixin; Wei, Yu; Wang, Lin; Uede, Toshimitsu; Li, Lanjuan; Diao, Hongyan

doi:10.1097/md.0000000000002606

Cited by 11 publications

(9 citation statements)

References 34 publications

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“…These observations confirmed the data reported by other studies where ECM pathways were significantly down-regulated in HPAI H7N9 and HPAI H5N1 [43]. A separate report also described that in human survivors of severe H7N9 infection, related proteins from the hydrolysis of fibronectin and collagens IV were found present in their plasma, suggesting that the ECM pathway was actively involved in remodeling damaged tissues [44].…”

Section: Discussionsupporting

confidence: 91%

A System Based-Approach to Examine Host Response during Infection with Influenza A Virus Subtype H7N9 in Human and Avian Cells

Taye

Chen

Yeo

et al. 2020

Cells

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Although the influenza A virus H7N9 subtype circulates within several avian species, it can also infect humans with a severe disease outcome. To better understand the biology of the H7N9 virus we examined the host response to infection in avian and human cells. In this study we used the A/Anhui/1/2013 strain, which was isolated during the first wave of the H7N9 epidemic. The H7N9 virus-infected both human (Airway Epithelial cells) and avian (Chick Embryo Fibroblast) cells, and each infected host transcriptome was examined with bioinformatic tools and compared with other representative avian and human influenza A virus subtypes. The H7N9 virus induced higher expression changes (differentially regulated genes) in both cell lines, with more prominent changes observed in avian cells. Ortholog mapping of differentially expression genes identified significant enriched common and cell-type pathways during H7N9 infections. This data confirmed our previous findings that different influenza A virus subtypes have virus-specific replication characteristics and anti-virus signaling in human and avian cells. In addition, we reported for the first time, the new HIPPO signaling pathway in avian cells, which we hypothesized to play a vital role to maintain the antiviral state of H7N9 virus-infected avian cells. This could explain the absence of disease symptoms in avian species that tested positive for the presence of H7N9 virus.

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Section: Discussionsupporting

confidence: 91%

A System Based-Approach to Examine Host Response during Infection with Influenza A Virus Subtype H7N9 in Human and Avian Cells

Taye

Chen

Yeo

et al. 2020

Cells

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“…Additionally, Chen, Zhou [ 22 ] also reported that EMC pathway was involved in H7N9 infection. On the other hand, Chen, Cui [ 23 ] found that higher plasma levels of hydrolysis of fibronectin and collagens IV related proteins in survivors of severe H7N9 infection and they hinted the ongoing tissue remodeling after severe H7N9 infection. Thus, the perturbed extracellular matrix pathway in cells might also hint the damaged tissue remodeling of cells, which devastated the fatality.…”

Section: Discussionmentioning

confidence: 99%

A meta-analysis of transcriptomic characterization revealed extracellular matrix pathway involved in the H5N1 and H7N9 infections

et al. 2017

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Avian-origin H5N1 and H7N9 influenza A viruses are capable of causing lethal infection in humans, with serious lung pathology and leading to acute respiratory distress syndrome. The contribution of host response associated with the poor prognosis of H5N1 and H7N9 infections remains unclear. The aim of this study was to identify the host factors involved in the high pathogenicity of H5N1 and H7N9 by a systematical meta-analysis. The RNA-seq datasets related to H5N1, H7N9, and H1N1 infections with time series were retrieved from GEO. After merging the data from different series, ComBat was used to adjust the known variances from different batches. The transcription factors binding the genes in each cluster were predicted by PASTAA. We figured out the genes that were differentially expressed at any time point in samples infected with H5N1, H7N9, or H1N1. The analysis of biological function showed that genes related with cytokine were up-regulated in all three viruses. However, genes associated with carbon metabolism were found exclusively down-regulated in H7N9 and the extracellular matrix pathway were only enriched in H5N1 and H7N9. To summary, our study suggested that the extracellular matrix might be associated with the high fatality of H5N1 and H7N9 viruses in humans.

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“…These results suggested that persistent abnormal MDSCs, including G-MDSCs and M-MDSCs, may be accompanied by a persistent state of “immunoparalysis”. Chen et al reported that in severe H7N9 patients, the total lymphocyte count and percentages of different lymphocyte subtypes returned to normal levels 1 month post-infection, while 3 months were needed for the normalization of CD14 + HLA-DR lo/neg MDSCs [ 30 ]. Unfortunately, our study did not record when the CD14 + HLA-DR lo/neg MDSC frequency of COVID-19 patients returned to normal levels.…”

Section: Discussionmentioning

confidence: 99%

Elevated frequencies of CD14+HLA-DRlo/neg MDSCs in COVID-19 patients

Xue

Jiang

Zhao

et al. 2021

Aging

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Background: The immune responses, hyper-inflammation or immunosuppression, may be closely related to COVID-19 progression. We aimed to evaluate the changes of frequency of CD14 + HLA-DR lo/neg MDSCs, a population of cells with potent immunosuppressive capacity, in COVID-19 patients. Methods: The levels of CD14 + HLA-DR lo/neg MDSCs were determined by flow cytometry in 27 COVID-19 patients, and their association with clinical characteristics and laboratory data were analyzed. Results: The frequency of CD14 + HLA-DR lo/neg MDSCs was elevated in COVID-19 patients, particularly severe patients. A follow-up comparison revealed a decline of CD14 + HLA-DR lo/neg MDSCs percentages in most patients 1 day after testing negative for SARS-CoV-2 nucleic acid, but the levels of CD14 + HLA-DR lo/neg MDSCs were still greater than 50.0% in 3 ICU patients 4-10 days after negative SARS-CoV-2 results. Elevated frequency of CD14 + HLA-DR lo/neg MDSCs was positively correlated with oropharyngeal viral loads and length of hospital stay, while negatively correlated with lymphocyte counts and serum albumin. Moreover, strong correlations were observed between the frequency of CD14 + HLA-DR lo/neg MDSCs and T cell subsets, NK cell counts, and B cell percentages. The frequency of CD14 + HLA-DR lo/neg MDSCs could be used as a predictor of COVID-19 severity. Conclusions: A high frequency of CD14 + HLA-DR lo/neg MDSCs, especially in severe patients, may indicate an immunoparalysis status and could be a predictor of disease severity and prognosis.

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Severe Infection With Avian Influenza A Virus is Associated With Delayed Immune Recovery in Survivors

Abstract: Supplemental Digital Content is available in the text

Cited by 11 publications

References 34 publications

A System Based-Approach to Examine Host Response during Infection with Influenza A Virus Subtype H7N9 in Human and Avian Cells

A System Based-Approach to Examine Host Response during Infection with Influenza A Virus Subtype H7N9 in Human and Avian Cells

A meta-analysis of transcriptomic characterization revealed extracellular matrix pathway involved in the H5N1 and H7N9 infections

Elevated frequencies of CD14+HLA-DRlo/neg MDSCs in COVID-19 patients

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