Anionic Pulmonary Surfactant Lipid Treatment Inhibits Rhinovirus A Infection of the Human Airway Epithelium
Rhinoviruses (RVs) are major instigators of acute exacerbations of asthma, COPD, and other respiratory diseases. RVs are categorized into three species (RV-A, RV-B, and RV-C), which comprise more than 160 serotypes, making it difficult to develop an effective vaccine. Currently, no effective treatme...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-03-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/15/3/747 |
| _version_ | 1797608593597399040 |
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| author | Mari Numata Satria Sajuthi Yury A. Bochkov Jessica Loeffler Jamie Everman Eszter K. Vladar Riley A. Cooney Richard Lee Reinhardt Andrew H. Liu Max A. Seibold Dennis R. Voelker |
| author_facet | Mari Numata Satria Sajuthi Yury A. Bochkov Jessica Loeffler Jamie Everman Eszter K. Vladar Riley A. Cooney Richard Lee Reinhardt Andrew H. Liu Max A. Seibold Dennis R. Voelker |
| author_sort | Mari Numata |
| collection | DOAJ |
| description | Rhinoviruses (RVs) are major instigators of acute exacerbations of asthma, COPD, and other respiratory diseases. RVs are categorized into three species (RV-A, RV-B, and RV-C), which comprise more than 160 serotypes, making it difficult to develop an effective vaccine. Currently, no effective treatment for RV infection is available. Pulmonary surfactant is an extracellular complex of lipids and proteins that plays a central role in regulating innate immunity in the lung. The minor pulmonary surfactant lipids, palmitoyl-oleoyl-phosphatidylglycerol (POPG) and phosphatidylinositol (PI), are potent regulators of inflammatory processes and exert antiviral activity against respiratory syncytial virus (RSV) and influenza A viruses (IAV). In the current study, we examined the potencies of POPG and PI against rhinovirus A16 (RV-A16) in primary human airway epithelial cells (AECs) differentiated at an air–liquid interface (ALI). After AECs were infected with RV-A16, PI reduced the viral RNA copy number by 70% and downregulated (55–75%) the expression of antiviral (MDA5, IRF7, and IFN-lambda) and CXCL11 chemokine genes. In contrast, POPG only slightly decreased MDA5 (24%) and IRF7 (11%) gene expression but did not inhibit IFN-lambda gene expression or RV-A16 replication in AECs. However, both POPG and PI inhibited (50–80%) IL6 gene expression and protein secretion and CXCL11 protein secretion. PI treatment dramatically attenuated global gene expression changes induced by RV-A16 infection alone in AECs. The observed inhibitory effects were indirect and resulted mainly from the inhibition of virus replication. Cell-type enrichment analysis of viral-regulated genes opposed by PI treatment revealed the PI-inhibited viral induction of goblet cell metaplasia and the virus-induced downregulation of ciliated, club, and ionocyte cell types. Notably, the PI treatment also altered the ability of RV-A16 to regulate the expression of some phosphatidylinositol 4-kinase (<i>PI4K</i>); acyl-CoA-binding, domain-containing (<i>ACBD</i>); and low-density lipoprotein receptor (<i>LDLR</i>) genes that play critical roles in the formation and functioning of replication organelles (ROs) required for RV replication in host cells. These data suggest PI can be used as a potent, non-toxic, antiviral agent for RV infection prophylaxis and treatment. |
| first_indexed | 2024-03-11T05:45:25Z |
| format | Article |
| id | doaj.art-0ee3e5c3b3924c77b05a74178c0a5d80 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-11T05:45:25Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-0ee3e5c3b3924c77b05a74178c0a5d802023-11-17T14:23:47ZengMDPI AGViruses1999-49152023-03-0115374710.3390/v15030747Anionic Pulmonary Surfactant Lipid Treatment Inhibits Rhinovirus A Infection of the Human Airway EpitheliumMari Numata0Satria Sajuthi1Yury A. Bochkov2Jessica Loeffler3Jamie Everman4Eszter K. Vladar5Riley A. Cooney6Richard Lee Reinhardt7Andrew H. Liu8Max A. Seibold9Dennis R. Voelker10Department of Medicine, National Jewish Health, Denver, CO 80206, USACenter for Genes, Environment and Health, National Jewish Health, Denver, CO 80206, USADepartment of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USADepartment of Medicine, National Jewish Health, Denver, CO 80206, USACenter for Genes, Environment and Health, National Jewish Health, Denver, CO 80206, USADepartment of Medicine, University of Colorado School of Medicine, Aurora, CO 80045, USADepartment of Medicine, University of Colorado School of Medicine, Aurora, CO 80045, USADepartment of Immunology and Genomic Medicine, National Jewish Health, Denver, CO 80206, USASection of Pediatric Pulmonary & Sleep Medicine, Children’s Hospital Colorado and University of Colorado School of Medicine, Aurora, CO 80045, USACenter for Genes, Environment and Health, National Jewish Health, Denver, CO 80206, USADepartment of Medicine, National Jewish Health, Denver, CO 80206, USARhinoviruses (RVs) are major instigators of acute exacerbations of asthma, COPD, and other respiratory diseases. RVs are categorized into three species (RV-A, RV-B, and RV-C), which comprise more than 160 serotypes, making it difficult to develop an effective vaccine. Currently, no effective treatment for RV infection is available. Pulmonary surfactant is an extracellular complex of lipids and proteins that plays a central role in regulating innate immunity in the lung. The minor pulmonary surfactant lipids, palmitoyl-oleoyl-phosphatidylglycerol (POPG) and phosphatidylinositol (PI), are potent regulators of inflammatory processes and exert antiviral activity against respiratory syncytial virus (RSV) and influenza A viruses (IAV). In the current study, we examined the potencies of POPG and PI against rhinovirus A16 (RV-A16) in primary human airway epithelial cells (AECs) differentiated at an air–liquid interface (ALI). After AECs were infected with RV-A16, PI reduced the viral RNA copy number by 70% and downregulated (55–75%) the expression of antiviral (MDA5, IRF7, and IFN-lambda) and CXCL11 chemokine genes. In contrast, POPG only slightly decreased MDA5 (24%) and IRF7 (11%) gene expression but did not inhibit IFN-lambda gene expression or RV-A16 replication in AECs. However, both POPG and PI inhibited (50–80%) IL6 gene expression and protein secretion and CXCL11 protein secretion. PI treatment dramatically attenuated global gene expression changes induced by RV-A16 infection alone in AECs. The observed inhibitory effects were indirect and resulted mainly from the inhibition of virus replication. Cell-type enrichment analysis of viral-regulated genes opposed by PI treatment revealed the PI-inhibited viral induction of goblet cell metaplasia and the virus-induced downregulation of ciliated, club, and ionocyte cell types. Notably, the PI treatment also altered the ability of RV-A16 to regulate the expression of some phosphatidylinositol 4-kinase (<i>PI4K</i>); acyl-CoA-binding, domain-containing (<i>ACBD</i>); and low-density lipoprotein receptor (<i>LDLR</i>) genes that play critical roles in the formation and functioning of replication organelles (ROs) required for RV replication in host cells. These data suggest PI can be used as a potent, non-toxic, antiviral agent for RV infection prophylaxis and treatment.https://www.mdpi.com/1999-4915/15/3/747antiviralinnate immunityprimary human airway epithelial cellsreplication organellehuman phosphatidylinositol 4-kinases |
| spellingShingle | Mari Numata Satria Sajuthi Yury A. Bochkov Jessica Loeffler Jamie Everman Eszter K. Vladar Riley A. Cooney Richard Lee Reinhardt Andrew H. Liu Max A. Seibold Dennis R. Voelker Anionic Pulmonary Surfactant Lipid Treatment Inhibits Rhinovirus A Infection of the Human Airway Epithelium Viruses antiviral innate immunity primary human airway epithelial cells replication organelle human phosphatidylinositol 4-kinases |
| title | Anionic Pulmonary Surfactant Lipid Treatment Inhibits Rhinovirus A Infection of the Human Airway Epithelium |
| title_full | Anionic Pulmonary Surfactant Lipid Treatment Inhibits Rhinovirus A Infection of the Human Airway Epithelium |
| title_fullStr | Anionic Pulmonary Surfactant Lipid Treatment Inhibits Rhinovirus A Infection of the Human Airway Epithelium |
| title_full_unstemmed | Anionic Pulmonary Surfactant Lipid Treatment Inhibits Rhinovirus A Infection of the Human Airway Epithelium |
| title_short | Anionic Pulmonary Surfactant Lipid Treatment Inhibits Rhinovirus A Infection of the Human Airway Epithelium |
| title_sort | anionic pulmonary surfactant lipid treatment inhibits rhinovirus a infection of the human airway epithelium |
| topic | antiviral innate immunity primary human airway epithelial cells replication organelle human phosphatidylinositol 4-kinases |
| url | https://www.mdpi.com/1999-4915/15/3/747 |
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