IFP35 as a promising biomarker and therapeutic target for the syndromes induced by SARS-CoV-2 or influenza virus

Cell Rep. 2021 Dec 21;37(12):110126. doi: 10.1016/j.celrep.2021.110126. Epub 2021 Dec 3.

Abstract

Previous studies have shown that the high mortality caused by viruses such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza virus primarily results from complications of a cytokine storm. Therefore, it is critical to identify the key factors participating in the cytokine storm. Here we demonstrate that interferon-induced protein 35 (IFP35) plays an important role in the cytokine storm induced by SARS-CoV-2 and influenza virus infection. We find that the levels of serum IFP35 in individuals with SARS-CoV-2 correlates with severity of the syndrome. Using mouse model and cell assays, we show that IFP35 is released by lung epithelial cells and macrophages after SARS-CoV-2 or influenza virus infection. In addition, we show that administration of neutralizing antibodies against IFP35 considerably reduces lung injury and, thus, the mortality rate of mice exposed to viral infection. Our findings suggest that IFP35 serves as a biomarker and as a therapeutic target in virus-induced syndromes.

Keywords: COVID-19; IFP35; biomarker and therapeutic target; cytokine storm; influenza virus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing / administration & dosage
  • Biomarkers / blood
  • COVID-19 / blood*
  • COVID-19 / pathology
  • COVID-19 / physiopathology
  • COVID-19 Drug Treatment*
  • Disease Models, Animal
  • Humans
  • Inflammation / metabolism
  • Influenza, Human / blood*
  • Influenza, Human / drug therapy*
  • Influenza, Human / pathology
  • Intracellular Signaling Peptides and Proteins / blood*
  • Lung / metabolism
  • Lung / pathology
  • Macrophages / metabolism
  • Macrophages / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Patient Acuity
  • SARS-CoV-2 / physiology

Substances

  • Antibodies, Neutralizing
  • Biomarkers
  • IFI35 protein, human
  • IFP35 protein, mouse
  • Intracellular Signaling Peptides and Proteins