Pulmonary Surfactant Lipids Inhibit Infections with the Pandemic H1N1 Influenza Virus in Several Animal Models

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J Biol Chem. 2019 Dec 27. pii: jbc.RA119.012053. doi: 10.1074/jbc.RA119.012053. [Epub ahead of print] Pulmonary Surfactant Lipids Inhibit Infections with the Pandemic H1N1 Influenza Virus in Several Animal Models.

Numata M¹, Mitchell JR², Tipper JL³, Brand JD³, Trombley JE³, Nagashima Y⁴, Kandasamy P¹, Chu HW¹, Harrod KS³, Voelker DR⁵.
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1 National Jewish Heatlh, United States. 2 National Jewish Health, United States. 3 University of Alabama at Birmingham, United States. 4 Surgical Pathology, Tokyo Women's Medical University Hospital, Japan. 5 Department of Medicine, Program in Cell Biology, National Jewish Health, United States.

Abstract

The influenza A (H1N1)pdm09 outbreak in 2009 exemplified the problems accompanying the emergence of novel influenza A virus (IAV) strains and their unanticipated virulence in populations with no pre-existing immunity. Neuraminidase inhibitors (NAIs) are currently drugs of choice for intervention against IAV outbreaks, but there are concerns that NAI-resistant viruses can transmit to high-risk populations. These issues highlight the need for new approaches that address the annual influenza burden. In this study, we examined whether palmitoyl-oleoyl-phosphatidylglycerol (POPG) and phosphatidylinositol (PI) effectively antagonize (H1N1)pdm09 infection. POPG and PI markedly suppressed cytopathic effects and attenuated viral gene expression in (H1N1)pdm09-infected MDCK cells. POPG and PI bound to (H1N1)pdm09 with high affinity and disrupted viral spread from infected to non-infected cells in tissue culture and also reduced (H1N1)pdm09 propagation by a factor of 102 after viral infection was established in vitro. In a mouse infection model of (H1N1)pdm09, POPG and PI significantly reduced lung inflammation and viral burden. Of note, when mice were challenged with a typically lethal dose of 1000 plaque-forming units (pfu) of (H1N1)pdm09, survival after 10 days was 100% (14 of 14 mice) with the POPG treatment compared with 0% (0 of 14 mice) without this treatment. POPG also significantly reduced inflammatory infiltrates and the viral burden induced by (H1N1)pdm09 infection in a ferret model. These findings indicate that anionic phospholipids potently and efficiently disrupt influenza infections in animal models.
Published under license by The American Society for Biochemistry and Molecular Biology, Inc.


KEYWORDS:

Phopholipids; antiviral agent; host defense; inflammation; influenza; innate immunity; phosphatidylglycerol; phosphatidylinositol; pulmonary surfactant; treatments; virology

PMID: 31882535 DOI: 10.1074/jbc.RA119.012053
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