ArticleRespiratory research2017
Sirolimus alters lung pathology and viral load following influenza A virus infection.
Article in Respiratory research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 36 citations in OpenAlex.
- The ribosomal landscape in influenza A virus infection: from molecular mechanisms to clinical relevance.European respiratory review : an official journal of the European Respiratory Society · 2026Review
- Respiratory Syncytial Virus in Hematopoietic Cell Transplant Recipients: Clinical and Humoral Risk Factors for Infection.Open forum infectious diseases · 2026Article
- Mammalian Target of Rapamycin Complex 1 Activation in Macrophages Contributes to Persistent Lung Inflammation following Respiratory Tract Viral Infection.The American journal of pathology · 2024Article
- Myeloid Zfhx3 deficiency protects against hypercapnia-induced suppression of host defense against influenza A virus.JCI insight · 2024Article
- A multi-antigen vaccinia vaccine broadly protected mice against SARS-CoV-2 and influenza A virus while also targeting SARS-CoV-1 and MERS-CoV.Frontiers in immunology · 2024Article
- Immunometabolic Signature during Respiratory Viral Infection: A Potential Target for Host-Directed Therapies.Viruses · 2023Review
- Effect of Sirolimus/Metformin Co-Treatment on Hyperglycemia and Cellular Respiration in BALB/c Mice.International journal of molecular sciences · 2023Article
- Effect of Duvelisib, a Selective PI3K Inhibitor on Seizure Activity in Pentylenetetrazole-Induced Convulsions Animal Model.Neuroscience insights · 2023Article
- Rapalogs downmodulate intrinsic immunity and promote cell entry of SARS-CoV-2.The Journal of clinical investigation · 2022Article
- Development of a humanized HLA-A30 transgenic mouse model.Animal models and experimental medicine · 2022Article
- Influenza antivirals and animal models.FEBS open bio · 2022Review
- Successful combinatorial therapy of sirolimus and neuraminidase inhibitors in a patient with highly pathogenic avian influenza A (H5N6) virus: a case report.Annals of translational medicine · 2022Article
- Sirolimus combined with oseltamivir and corticosteroid treatment for a puerpera with severe pneumonia caused by 2009 pandemic H1N1: A case report.Biosafety and health · 2021Article
- Exacerbation of Influenza A Virus Disease Severity by Respiratory Syncytial Virus Co-Infection in a Mouse Model.Viruses · 2021Article
- Dysregulation in Akt/mTOR/HIF-1 signaling identified by proteo-transcriptomics of SARS-CoV-2 infected cells.Emerging microbes & infections · 2020Article
- Hypercapnia Suppresses Macrophage Antiviral Activity and Increases Mortality of Influenza A Infection via Akt1.Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- Galectin-1 Ameliorates Influenza A H1N1pdm09 Virus-Induced Acute Lung Injury.Frontiers in microbiology · 2020Article
- Efficacy and safety of low-dose Sirolimus in Lymphangioleiomyomatosis.Orphanet journal of rare diseases · 2018Article
- Delayed oseltamivir plus sirolimus treatment attenuates H1N1 virus-induced severe lung injury correlated with repressed NLRP3 inflammasome activation and inflammatory cell infiltration.PLoS pathogens · 2018Article
- The role of adjuvant immunomodulatory agents for treatment of severe influenza.Antiviral research · 2018Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundInhibitors of mTOR, such as sirolimus, have been shown to induce thymus involution and inflammatory lung disease in mice. The latter effect supports the role of this serine/threonine kinase in ameliorating lung inflammation. Other studies have shown sirolimus reduces/delays lung disease associated with various strains of influenza A virus (IAV). Thus, the effects of mTOR inhibitors on influenza infection deserve further studies.
methodsHere, we examined the changes in lung viral copies, pathology and pulmonary function associated with IAV (A/PR/8/34) infection in mice treated with sirolimus.
resultsBody weight loss peaked between days 6-11 post-infection and was more severe in IAV-infected mice that were administered sirolimus as compared to mice that received IAV alone (p = 0.030). Natural log viral gene copies, mean ± SD per mg lung tissue, in IAV-infected mice that were administered sirolimus were 17.31 ± 1.27 on day 4, 19.31 ± 7.46 on day 10, and 0 on day 25. The corresponding number of copies in mice that received IAV alone were 18.56 ± 0.95 on day 4 (p = 0.132), 1.52 ± 1.39 on day 10 (p = 0.008), and 0 on day 25. Lung pathology was evident on days 4, 10, and 25 post infection, with mean ± SD inflammatory score of 9.0 ± 4.5 in IAV-infected mice that were administered sirolimus, as compared to 11.5 ± 4.5 (p = 0.335) in mice received IAV alone (maximum score, 26.0). Impaired lung function was evident in IAV-infected mice on days 4 and 10, as demonstrated by increased airway resistance and decreased compliance.
conclusionsIn this model, the effects of sirolimus on influenza infection included severe weight loss and modified viral replication, respiratory function and lung inflammation. The adverse events associated with sirolimus treatment are consistent with its potent immunosuppressive activity and, thus, preclude its use in IAV infection.
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