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Am J Respir Cell Mol Biol. Phosphatidylglycerol Suppresses Influenza A Virus Infection
[Source: American Journal of Respiratory Cell and Molecular Biology, full text: (LINK). Abstract, edited.]
Am. J. Respir. Cell Mol. Biol. 2011, doi:10.1165/2011-0194OC
Submitted on June 10, 2011
Accepted on November 3, 2011
Phosphatidylglycerol Suppresses Influenza A Virus Infection
Mari Numata<SUP>1</SUP>, Pitchaimani Kandasamy<SUP>1</SUP>, Yoji Nagashima<SUP>2</SUP>, Janelle Posey<SUP>1</SUP>, Kevan Hartshorn<SUP>3</SUP>, David Woodland<SUP>4</SUP>, and Dennis R Voelker<SUP>1</SUP><SUP>*</SUP>
<SUP>1</SUP> Department of Medicine, Program in Cell Biology, National Jewish Health, Denver, Colorado, United States, <SUP>2</SUP> Department of Pathology, Yokohama City University School of Medicine, Yokohama, Japan, <SUP>3</SUP> Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, United States, <SUP>4</SUP> Trudeau Institute, Saranac, New York, United States
<SUP>*</SUP> To whom correspondence should be addressed. E-mail: voelkerd@NJHealth.org .
Influenza A virus (IAV) is a worldwide public health problem<SUP> </SUP>causing 500,000 deaths each year. Palmitoyl-oleoyl-phophatidylglycerol<SUP> </SUP>(POPG) is a minor component of pulmonary surfactant, which has<SUP> </SUP>recently been reported to exert potent regulatory functions<SUP> </SUP>upon the innate immune system. In this report we demonstrate<SUP> </SUP>that POPG acts as a strong anti-viral agent against IAV. POPG<SUP> </SUP>markedly attenuated IL-8 production and cell death induced by<SUP> </SUP>IAV in cultured human bronchial epithelial cells. The lipid<SUP> </SUP>also suppressed viral attachment to the plasma membrane and<SUP> </SUP>subsequent replication in MDCK cells. Two virus strains, H1N1-PR8-IAV<SUP> </SUP>and H3N2-IAV bind to POPG with high affinity but exhibit only<SUP> </SUP>low affinity interactions with the structurally related lipid<SUP> </SUP>palmitoyl-oleoyl-phosphatidylcholine. Intranasal inoculation<SUP> </SUP>of H1N1-PR8-IAV in mice, in the presence of POPG, markedly suppressed<SUP> </SUP>the development of inflammatory cell infiltrates and the induction<SUP> </SUP>of IFN-
recovered in bronchoalveolar lavage, and viral titers<SUP> </SUP>recovered from the lungs after 5 days of infection. These findings<SUP> </SUP>identify supplementary POPG as a potentially important new approach<SUP> </SUP>for treatment of IAV infections.
<SUP></SUP>Key words: Antiviral ? Innate immunity ? Pulmonary surfactant
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Am. J. Respir. Cell Mol. Biol. 2011, doi:10.1165/2011-0194OC
Submitted on June 10, 2011
Accepted on November 3, 2011
Phosphatidylglycerol Suppresses Influenza A Virus Infection
Mari Numata<SUP>1</SUP>, Pitchaimani Kandasamy<SUP>1</SUP>, Yoji Nagashima<SUP>2</SUP>, Janelle Posey<SUP>1</SUP>, Kevan Hartshorn<SUP>3</SUP>, David Woodland<SUP>4</SUP>, and Dennis R Voelker<SUP>1</SUP><SUP>*</SUP>
<SUP>1</SUP> Department of Medicine, Program in Cell Biology, National Jewish Health, Denver, Colorado, United States, <SUP>2</SUP> Department of Pathology, Yokohama City University School of Medicine, Yokohama, Japan, <SUP>3</SUP> Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, United States, <SUP>4</SUP> Trudeau Institute, Saranac, New York, United States
<SUP>*</SUP> To whom correspondence should be addressed. E-mail: voelkerd@NJHealth.org .
Influenza A virus (IAV) is a worldwide public health problem<SUP> </SUP>causing 500,000 deaths each year. Palmitoyl-oleoyl-phophatidylglycerol<SUP> </SUP>(POPG) is a minor component of pulmonary surfactant, which has<SUP> </SUP>recently been reported to exert potent regulatory functions<SUP> </SUP>upon the innate immune system. In this report we demonstrate<SUP> </SUP>that POPG acts as a strong anti-viral agent against IAV. POPG<SUP> </SUP>markedly attenuated IL-8 production and cell death induced by<SUP> </SUP>IAV in cultured human bronchial epithelial cells. The lipid<SUP> </SUP>also suppressed viral attachment to the plasma membrane and<SUP> </SUP>subsequent replication in MDCK cells. Two virus strains, H1N1-PR8-IAV<SUP> </SUP>and H3N2-IAV bind to POPG with high affinity but exhibit only<SUP> </SUP>low affinity interactions with the structurally related lipid<SUP> </SUP>palmitoyl-oleoyl-phosphatidylcholine. Intranasal inoculation<SUP> </SUP>of H1N1-PR8-IAV in mice, in the presence of POPG, markedly suppressed<SUP> </SUP>the development of inflammatory cell infiltrates and the induction<SUP> </SUP>of IFN-
recovered in bronchoalveolar lavage, and viral titers<SUP> </SUP>recovered from the lungs after 5 days of infection. These findings<SUP> </SUP>identify supplementary POPG as a potentially important new approach<SUP> </SUP>for treatment of IAV infections. <SUP></SUP>Key words: Antiviral ? Innate immunity ? Pulmonary surfactant