Dataset Information

Sirolimus alters lung pathology and viral load following influenza A virus infection.

ABSTRACT: Inhibitors 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.Here, 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.Body 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.In 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.

SUBMITTER: Alsuwaidi AR

PROVIDER: S-EPMC5504865 | biostudies-other | 2017 Jul

REPOSITORIES: biostudies-other

ACCESS DATA

Similar Datasets

Project description:Alterations in the composition of the gut microbiota have profound effects on human health. Consequently, there is great interest in identifying, characterizing, and understanding factors that initiate these changes. Despite their high prevalence, studies have only recently begun to investigate how viral lung infections have an impact on the gut microbiota. There is also considerable interest in whether the gut microbiota could be manipulated during vaccination to improve efficacy. In this highly controlled study, we aimed to establish the effect of viral lung infection on gut microbiota composition and the gut environment using mouse models of common respiratory pathogens respiratory syncytial virus (RSV) and influenza virus. This was then compared to the effect of live attenuated influenza virus (LAIV) vaccination. Both RSV and influenza virus infection resulted in significantly altered gut microbiota diversity, with an increase in Bacteroidetes and a concomitant decrease in Firmicutes phyla abundance. Although the increase in the Bacteroidetes phylum was consistent across several experiments, differences were observed at the family and operational taxonomic unit level. This suggests a change in gut conditions after viral lung infection that favors Bacteroidetes outgrowth but not individual families. No change in gut microbiota composition was observed after LAIV vaccination, suggesting that the driver of gut microbiota change is specific to live viral infection. Viral lung infections also resulted in an increase in fecal lipocalin-2, suggesting low-grade gut inflammation, and colonic Muc5ac levels. Owing to the important role that mucus plays in the gut environment, this may explain the changes in microbiota composition observed. This study demonstrates that the gut microbiota and the gut environment are altered following viral lung infections and that these changes are not observed during vaccination. Whether increased mucin levels and gut inflammation drive, or are a result of, these changes is still to be determined.

Dataset Information

Sirolimus alters lung pathology and viral load following influenza A virus infection.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets