title: Phosphatidylglycerol suppresses influenza A virus infection.
abstract: Influenza A virus (IAV) is a worldwide public health problem causing 500,000 deaths each year. Palmitoyl-oleoyl-phosphatidylglycerol (POPG) is a minor component of pulmonary surfactant, which has recently been reported to exert potent regulatory functions upon the innate immune system. In this article, we demonstrate that POPG acts as a strong antiviral agent against IAV. POPG markedly attenuated IL-8 production and cell death induced by IAV in cultured human bronchial epithelial cells. The lipid also suppressed viral attachment to the plasma membrane and subsequent replication in Madin-Darby canine kidney cells. Two virus strains, H1N1-PR8-IAV and H3N2-IAV, bind to POPG with high affinity, but exhibit only low-affinity interactions with the structurally related lipid, palmitoyl-oleoyl-phosphatidylcholine. Intranasal inoculation of H1N1-PR8-IAV in mice, in the presence of POPG, markedly suppressed the development of inflammatory cell infiltrates, the induction of IFN-γ recovered in bronchoalveolar lavage, and viral titers recovered from the lungs after 5 days of infection. These findings identify supplementary POPG as a potentially important new approach for treatment of IAV infections.
authors: Department of Medicine, Program in Cell Biology, National Jewish Health, Denver, CO 80206, USA.
authors: Mari
authors: M
authors: Numata
authors: Pitchaimani
authors: P
authors: Kandasamy
authors: Yoji
authors: Y
authors: Nagashima
authors: Janelle
authors: J
authors: Posey
authors: Kevan
authors: K
authors: Hartshorn
authors: David
authors: D
authors: Woodland
authors: Dennis R
authors: DR
authors: Voelker
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D001980:Bronchi / Q000166:cytology / Q000187:drug effects / Q000821:virology; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000821:virology; D005260:Female; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects / Q000472:pathogenicity; D053122:Influenza A Virus, H3N2 Subtype / Q000187:drug effects / Q000472:pathogenicity; D009980:Influenza A virus / Q000187:drug effects* / Q000378:metabolism / Q000472:pathogenicity*; D007251:Influenza, Human / Q000188:drug therapy* / Q000821:virology; D016209:Interleukin-8 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000188:drug therapy / Q000821:virology; D010715:Phosphatidylglycerols / Q000494:pharmacology*; D010743:Phospholipids / Q000378:metabolism; D014764:Viral Proteins / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D016207:Cytokines; D016209:Interleukin-8; D010715:Phosphatidylglycerols; D010743:Phospholipids; D014764:Viral Proteins