Summary of Study ST003290
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR002042. The data can be accessed directly via it's Project DOI: 10.21228/M8NV6P This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
| Study ID | ST003290 |
| Study Title | High expression of oleoyl-ACP-hydrolase underpins life-threatening respiratory viral diseases |
| Study Summary | Although respiratory viral infections cause significant morbidity and mortality, it is unclear why some individuals succumb to severe disease. In patients hospitalized with avian A(H7N9) influenza, we investigated early drivers underpinning hypercytokinemia and fatal disease. Our transcriptomics studies identified differential expression of 10 early host genes, defined by 16 probe sets, between patients who recovered and died. Seven probe sets were specific for the same host gene encoding for a key enzyme mediating free fatty acid production, oleoyl-ACP-hydrolase (OLAH). High OLAH levels in fatal A(H7N9) patients were detected early after hospital admission and persisted until patients died. Conversely, patients who recovered had minimal OLAH expression throughout their hospital stay. High OLAH levels were also detected in patients hospitalized for severe infections with seasonal influenza virus, SARS-CoV-2, respiratory syncytial virus (RSV) and for multisystem inflammatory syndrome in children (MIS-C), while the main catalytic product of OLAH, oleic acid, was increased in hospitalized compared to ambulatory patients. Among healthy individuals and those with mild infections, however, OLAH was minimally detected. To understand how OLAH drives disease severity, we generated olah deficient mice. In contrast to wild-type mice, lethal influenza infection of olah-/- mice led to survival, milder disease, and markedly reduced lung viral loads, tissue damage, infection-driven pulmonary innate cell infiltration and inflammatory milieu. This phenotype was associated with differential lipid droplet dynamics, and reduced viral infection and inflammatory responses in macrophages. Supplementation of oleic acid, the main product of OLAH, increased influenza infection of macrophages and their inflammatory potential. Increased infectivity in the presence of olah was dependent on lipid droplet usage. Our findings define how expression of the key host enzyme, OLAH, drives life-threatening inflammation associated with respiratory viruses and propose OLAH as a potential early target for diagnosis and treatment of patients with severe disease. |
| Institute | Peter Doherty Institute for Infection and Immunity |
| Last Name | Chua |
| First Name | Brendon |
| Address | 792 Elizabeth St, Melbourne VIC 3000 |
| bychua@unimelb.edu.au | |
| Phone | +61383441130 |
| Submit Date | 2024-06-26 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | mzML |
| Analysis Type Detail | LC-MS |
| Release Date | 2024-08-22 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Combined analysis:
| Analysis ID | AN005388 | AN005389 |
|---|---|---|
| Analysis type | MS | MS |
| Chromatography type | Reversed phase | Reversed phase |
| Chromatography system | Thermo Vanquish | Thermo Vanquish |
| Column | Waters ACQUITY UPLC HSS T3 (150 x 1mm,1.8um) | Waters ACQUITY UPLC HSS T3 (150 x 1mm,1.8um) |
| MS Type | ESI | ESI |
| MS instrument type | Orbitrap | Orbitrap |
| MS instrument name | Thermo Fusion Tribrid Orbitrap | Thermo Fusion Tribrid Orbitrap |
| Ion Mode | POSITIVE | NEGATIVE |
| Units | pmol/mg lung tissue | pmol/mg lung tissue |
MS:
| MS ID: | MS005115 |
| Analysis ID: | AN005388 |
| Instrument Name: | Thermo Fusion Tribrid Orbitrap |
| Instrument Type: | Orbitrap |
| MS Type: | ESI |
| MS Comments: | Top speed data-dependent scan with a cycle time of 1s was used. Within each cycle, a full-scan MS-spectra were acquired firstly in the Orbitrap at a mass resolving power of 120,000 across an m/z range of 300–2000 using quadrupole isolation, followed by higher-energy collisional dissociation (HCD)-MS/MS at a mass resolving power of 15,000 (at m/z 200) and a normalized collision energy (NCE) of 27% at positive mode and 30% in negative mode with an m/z isolation window of 1. |
| Ion Mode: | POSITIVE |
| MS ID: | MS005116 |
| Analysis ID: | AN005389 |
| Instrument Name: | Thermo Fusion Tribrid Orbitrap |
| Instrument Type: | Orbitrap |
| MS Type: | ESI |
| MS Comments: | Top speed data-dependent scan with a cycle time of 1s was used. Within each cycle, a full-scan MS-spectra were acquired firstly in the Orbitrap at a mass resolving power of 120,000 across an m/z range of 300–2000 using quadrupole isolation, followed by higher-energy collisional dissociation (HCD)-MS/MS at a mass resolving power of 15,000 (at m/z 200) and a normalized collision energy (NCE) of 27% at positive mode and 30% in negative mode with an m/z isolation window of 1. |
| Ion Mode: | NEGATIVE |
