tetano
Editor, Senior Moderator
J Biol Chem. 2019 Dec 27. pii: jbc.RA119.012053. doi: 10.1074/jbc.RA119.012053. [Epub ahead of print] [h=1]Pulmonary Surfactant Lipids Inhibit Infections with the Pandemic H1N1 Influenza Virus in Several Animal Models.[/h]
Numata M[SUP]1[/SUP], Mitchell JR[SUP]2[/SUP], Tipper JL[SUP]3[/SUP], Brand JD[SUP]3[/SUP], Trombley JE[SUP]3[/SUP], Nagashima Y[SUP]4[/SUP], Kandasamy P[SUP]1[/SUP], Chu HW[SUP]1[/SUP], Harrod KS[SUP]3[/SUP], Voelker DR[SUP]5[/SUP].
[h=3]Author information[/h] 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.
[h=3]Abstract[/h] 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.
[h=4]KEYWORDS:[/h] 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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Numata M[SUP]1[/SUP], Mitchell JR[SUP]2[/SUP], Tipper JL[SUP]3[/SUP], Brand JD[SUP]3[/SUP], Trombley JE[SUP]3[/SUP], Nagashima Y[SUP]4[/SUP], Kandasamy P[SUP]1[/SUP], Chu HW[SUP]1[/SUP], Harrod KS[SUP]3[/SUP], Voelker DR[SUP]5[/SUP].
[h=3]Author information[/h] 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.
[h=3]Abstract[/h] 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.
[h=4]KEYWORDS:[/h] Phopholipids; antiviral agent; host defense; inflammation; influenza; innate immunity; phosphatidylglycerol; phosphatidylinositol; pulmonary surfactant; treatments; virology
PMID: 31882535 DOI: 10.1074/jbc.RA119.012053
Free full text