tetano
Editor, Senior Moderator
J Virol
. 2020 Nov 11;JVI.01753-20.
doi: 10.1128/JVI.01753-20. Online ahead of print.
Influenza neuraminidase engages CD83 and promotes pulmonary injury
Ning Ma[SUP] 1 [/SUP], Xingjie Li[SUP] 1 2 [/SUP], Hongyu Jiang[SUP] 1 2 [/SUP], Yulong Dai[SUP] 1 [/SUP], Guofeng Xu[SUP] 1 [/SUP], Zongde Zhang[SUP] 3 2 [/SUP]
Affiliations
Abstract
Influenza A viruses cause severe respiratory illnesses in humans and animals. Overreaction of the innate immune response to influenza infection results in hypercytokinemia, which is responsible for mortality and morbidity. However, the mechanism by which influenza induces hypercytokinemia is not fully understood. In this study, we established a mouse-adapted H9N2 virus MA01 to evaluate the innate immune response to influenza in the lung. MA01 infection caused high levels of cytokine release, enhanced pulmonary injury in mice, and upregulated CD83 protein in dendritic cells and macrophages in the lung. Influenza neuraminidase unmasked CD83 protein and contributed to high cytokine levels. Furthermore, we provide evidence that CD83 is a sialylated glycoprotein. Neuraminidase treatment enhanced LPS-stimulated NF-κB activation in RAW264.7 cells. Anti-CD83 treatment alleviated influenza virus-induced lung injury in mice. Our study indicates that influenza neuraminidase modulates CD83 status and contributes to the "cytokine storm", which may suggest a new approach to curb this immune injury.IMPORTANCE The massive release of circulating mediators of inflammation is responsible for lung injury during influenza A virus infection. This phenomenon refers to the"cytokine storm". However, the mechanism by which influenza induces"cytokine storm" is not fully understood. In this study, we have shown that neuraminidase unmasked CD83 protein in the lung and contributed to high cytokine levels. Anti-CD83 treatment could diminish immune damage to lung tissue. The NA-CD83 axis may represent a target for an interrupt of influenza induced lung damage.
. 2020 Nov 11;JVI.01753-20.
doi: 10.1128/JVI.01753-20. Online ahead of print.
Influenza neuraminidase engages CD83 and promotes pulmonary injury
Ning Ma[SUP] 1 [/SUP], Xingjie Li[SUP] 1 2 [/SUP], Hongyu Jiang[SUP] 1 2 [/SUP], Yulong Dai[SUP] 1 [/SUP], Guofeng Xu[SUP] 1 [/SUP], Zongde Zhang[SUP] 3 2 [/SUP]
Affiliations
- PMID: 33177200
- DOI: 10.1128/JVI.01753-20
Abstract
Influenza A viruses cause severe respiratory illnesses in humans and animals. Overreaction of the innate immune response to influenza infection results in hypercytokinemia, which is responsible for mortality and morbidity. However, the mechanism by which influenza induces hypercytokinemia is not fully understood. In this study, we established a mouse-adapted H9N2 virus MA01 to evaluate the innate immune response to influenza in the lung. MA01 infection caused high levels of cytokine release, enhanced pulmonary injury in mice, and upregulated CD83 protein in dendritic cells and macrophages in the lung. Influenza neuraminidase unmasked CD83 protein and contributed to high cytokine levels. Furthermore, we provide evidence that CD83 is a sialylated glycoprotein. Neuraminidase treatment enhanced LPS-stimulated NF-κB activation in RAW264.7 cells. Anti-CD83 treatment alleviated influenza virus-induced lung injury in mice. Our study indicates that influenza neuraminidase modulates CD83 status and contributes to the "cytokine storm", which may suggest a new approach to curb this immune injury.IMPORTANCE The massive release of circulating mediators of inflammation is responsible for lung injury during influenza A virus infection. This phenomenon refers to the"cytokine storm". However, the mechanism by which influenza induces"cytokine storm" is not fully understood. In this study, we have shown that neuraminidase unmasked CD83 protein in the lung and contributed to high cytokine levels. Anti-CD83 treatment could diminish immune damage to lung tissue. The NA-CD83 axis may represent a target for an interrupt of influenza induced lung damage.