Prion Protein is a Novel Modulator of Influenza: Potential Implications for Anti-Influenza Therapeutics

Curr Issues Mol Biol. 2020:37:21-32. doi: 10.21775/cimb.037.021. Epub 2019 Dec 9.

Abstract

Worldwide spread of influenza A virus (IAV) strains, which are resistant to currently available anti- influenza agents such as viral neuraminidase inhibitors, has encouraged identification of new target molecules for anti-influenza agents. Reactive oxygen species (ROS) causing oxidative stress play a pivotal role in the pathogenesis of lung injuries induced by infection with IAVs, therefore suggesting that anti-oxidative therapeutics targeting cellular molecules could be beneficial against IAV infection without inducing drug-resistant IAV strains. We recently found that the normal cellular prion protein, PrPC, whose conformational conversion into the amyloidogenic isoform, PrPSc, in the brain is a key pathogenic event in prion diseases, is expressed by lung epithelial cells and exerts a protective role against IAV infection in mice by reducing ROS in infected lungs. The Cu content and activity of anti- oxidative enzyme Cu/Zn-superoxide dismutase, or SOD1, were lower in the lungs of PrPC-knockout mice, suggesting that the anti-oxidative activity of PrPC is probably attributable to its function of activating SOD1 through regulating Cu content in lungs. Here, we introduce PrPC as a novel modulator of influenza and its potential implication for anti-oxidative therapies for IAV infection. We also introduce other candidate targets reported for anti- oxidative anti-influenza therapies.

Publication types

  • Review

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Antiviral Agents / pharmacology*
  • Antiviral Agents / therapeutic use
  • Host-Pathogen Interactions
  • Humans
  • Influenza A virus / drug effects*
  • Influenza A virus / physiology*
  • Influenza, Human / drug therapy
  • Influenza, Human / genetics
  • Influenza, Human / metabolism
  • Influenza, Human / virology*
  • Oxidation-Reduction / drug effects
  • Prion Proteins / pharmacology*
  • Protective Agents / pharmacology
  • Reactive Oxygen Species / metabolism
  • Virus Replication / drug effects

Substances

  • Antioxidants
  • Antiviral Agents
  • Prion Proteins
  • Protective Agents
  • Reactive Oxygen Species