Influenza A virus-induced autophagy contributes to enhancement of virus infectivity by SOD1 downregulation in alveolar epithelial cells

Kwang Il Jung, Chul Woong Pyo, Sang-Yun Choi

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9 Citations (Scopus)

Abstract

Infection with influenza A virus (IAV) A/WSN/1933 (H1N1) causes oxidative stress and severe lung injury. We have demonstrated that the generation of reactive oxygen species (ROS) during IAV infection is tightly regulated by superoxide dismutase 1 (SOD1) and correlated with viral replication in alveolar epithelial cells. However, the molecular mechanism underlying SOD1 reduction during IAV infection is uncertain. Here we demonstrate that the autophagy pathway is activated by IAV infection and involved in enhanced ROS generation in the early phase of infection. We observed that IAV infection induced autophagic vacuolation, leading to autophagic degradation of cellular proteins, including the protease sensitive antioxidant SOD1. Silencing of the microtubule-associated protein 1A/1B-light chain 3 (LC3) gene in A549 cells supported the critical role of autophagy in the ROS increase. The decrease in viral titer and viral polymerase activity caused by LC3 silencing or the autophagy inhibitor clearly evidenced the involvement of autophagy in the control of ROS generation and viral infectivity. Therefore, we concluded that early stage IAV infection induces autophagic degradation of antioxidant enzyme SOD1, thereby contributing to increased ROS generation and viral infectivity in alveolar epithelial cells.

Original languageEnglish
Pages (from-to)960-966
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume498
Issue number4
DOIs
Publication statusPublished - 2018 Apr 15

Fingerprint

Alveolar Epithelial Cells
Influenza A virus
Autophagy
Viruses
Superoxide Dismutase
Virus Diseases
Down-Regulation
Reactive Oxygen Species
Antioxidants
Light
Degradation
Oxidative stress
Microtubule-Associated Proteins
Lung Injury
Infection
Proteolysis
Superoxide Dismutase-1
Epithelial Cells
Oxidative Stress
Peptide Hydrolases

Keywords

  • Autophagy
  • Infectivity
  • Influenza
  • ROS
  • SOD1

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

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abstract = "Infection with influenza A virus (IAV) A/WSN/1933 (H1N1) causes oxidative stress and severe lung injury. We have demonstrated that the generation of reactive oxygen species (ROS) during IAV infection is tightly regulated by superoxide dismutase 1 (SOD1) and correlated with viral replication in alveolar epithelial cells. However, the molecular mechanism underlying SOD1 reduction during IAV infection is uncertain. Here we demonstrate that the autophagy pathway is activated by IAV infection and involved in enhanced ROS generation in the early phase of infection. We observed that IAV infection induced autophagic vacuolation, leading to autophagic degradation of cellular proteins, including the protease sensitive antioxidant SOD1. Silencing of the microtubule-associated protein 1A/1B-light chain 3 (LC3) gene in A549 cells supported the critical role of autophagy in the ROS increase. The decrease in viral titer and viral polymerase activity caused by LC3 silencing or the autophagy inhibitor clearly evidenced the involvement of autophagy in the control of ROS generation and viral infectivity. Therefore, we concluded that early stage IAV infection induces autophagic degradation of antioxidant enzyme SOD1, thereby contributing to increased ROS generation and viral infectivity in alveolar epithelial cells.",
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AU - Jung, Kwang Il

AU - Pyo, Chul Woong

AU - Choi, Sang-Yun

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N2 - Infection with influenza A virus (IAV) A/WSN/1933 (H1N1) causes oxidative stress and severe lung injury. We have demonstrated that the generation of reactive oxygen species (ROS) during IAV infection is tightly regulated by superoxide dismutase 1 (SOD1) and correlated with viral replication in alveolar epithelial cells. However, the molecular mechanism underlying SOD1 reduction during IAV infection is uncertain. Here we demonstrate that the autophagy pathway is activated by IAV infection and involved in enhanced ROS generation in the early phase of infection. We observed that IAV infection induced autophagic vacuolation, leading to autophagic degradation of cellular proteins, including the protease sensitive antioxidant SOD1. Silencing of the microtubule-associated protein 1A/1B-light chain 3 (LC3) gene in A549 cells supported the critical role of autophagy in the ROS increase. The decrease in viral titer and viral polymerase activity caused by LC3 silencing or the autophagy inhibitor clearly evidenced the involvement of autophagy in the control of ROS generation and viral infectivity. Therefore, we concluded that early stage IAV infection induces autophagic degradation of antioxidant enzyme SOD1, thereby contributing to increased ROS generation and viral infectivity in alveolar epithelial cells.

AB - Infection with influenza A virus (IAV) A/WSN/1933 (H1N1) causes oxidative stress and severe lung injury. We have demonstrated that the generation of reactive oxygen species (ROS) during IAV infection is tightly regulated by superoxide dismutase 1 (SOD1) and correlated with viral replication in alveolar epithelial cells. However, the molecular mechanism underlying SOD1 reduction during IAV infection is uncertain. Here we demonstrate that the autophagy pathway is activated by IAV infection and involved in enhanced ROS generation in the early phase of infection. We observed that IAV infection induced autophagic vacuolation, leading to autophagic degradation of cellular proteins, including the protease sensitive antioxidant SOD1. Silencing of the microtubule-associated protein 1A/1B-light chain 3 (LC3) gene in A549 cells supported the critical role of autophagy in the ROS increase. The decrease in viral titer and viral polymerase activity caused by LC3 silencing or the autophagy inhibitor clearly evidenced the involvement of autophagy in the control of ROS generation and viral infectivity. Therefore, we concluded that early stage IAV infection induces autophagic degradation of antioxidant enzyme SOD1, thereby contributing to increased ROS generation and viral infectivity in alveolar epithelial cells.

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KW - Infectivity

KW - Influenza

KW - ROS

KW - SOD1

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