Interferon-gamma inhibits influenza A virus cellular attachment by reducing sialic acid cluster size
Carol Ho-Yan Fong,
Lu Lu,
Lin-Lei Chen,
Man-Lung Yeung,
Anna Jinxia Zhang,
Hanjun Zhao,
Kwok-Yung Yuen,
Kelvin Kai-Wang To
Affiliations
Carol Ho-Yan Fong
State Key Laboratory for Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People’s Republic of China; Corresponding author
Lu Lu
State Key Laboratory for Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People’s Republic of China
Lin-Lei Chen
State Key Laboratory for Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People’s Republic of China
Man-Lung Yeung
State Key Laboratory for Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People’s Republic of China
Anna Jinxia Zhang
State Key Laboratory for Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People’s Republic of China
Hanjun Zhao
State Key Laboratory for Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People’s Republic of China
Kwok-Yung Yuen
State Key Laboratory for Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People’s Republic of China; Department of Microbiology, Queen Mary Hospital, Pokfulam, Hong Kong Island, People’s Republic of China
Kelvin Kai-Wang To
State Key Laboratory for Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People’s Republic of China; Department of Microbiology, Queen Mary Hospital, Pokfulam, Hong Kong Island, People’s Republic of China; Corresponding author
Summary: The mucosal antiviral role of type I and III interferon in influenza virus infection is well established. However, much less is known about the antiviral mechanism of type II interferon (interferon-gamma). Here, we revealed an antiviral mechanism of interferon-gamma by inhibiting influenza A virus (IAV) attachment. By direct stochastic optical reconstruction microscopy, confocal microscopy, and flow cytometry, we have shown that interferon-gamma reduced the size of α-2,3 and α-2,6-linked sialic acid clusters, without changing the sialic acid or epidermal growth factor receptor expression levels, or the sialic acid density within cluster on the cell surface of A549 cells. Reversing the effect of interferon-gamma on sialic acid clustering by jasplakinolide reverted the cluster size, improved IAV attachment and replication. Our findings showed the importance of sialic acid clustering in IAV attachment and infection. We also demonstrated the interference of sialic acid clustering as an anti-IAV mechanism of IFN-gamma for IAV infection.
