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Oral Antibiotic Treatment of Mice Exacerbates the Disease Severity of Multiple Flavivirus Infections.

ABSTRACT: Although the outcome of flavivirus infection can vary from asymptomatic to lethal, environmental factors modulating disease severity are poorly defined. Here, we observed increased susceptibility of mice to severe West Nile (WNV), Dengue, and Zika virus infections after treatment with oral antibiotics (Abx) that depleted the gut microbiota. Abx treatment impaired the development of optimal T cell responses, with decreased levels of WNV-specific CD8+ T cells associated with increased infection and immunopathology. Abx treatments that resulted in enhanced WNV susceptibility generated changes in the overall structure of the gut bacterial community and in the abundance of specific bacterial taxa. As little as 3 days of treatment with ampicillin was sufficient to alter host immunity and WNV outcome. Our results identify oral Abx therapy as a potential environmental determinant of systemic viral disease, and they raise the possibility that perturbation of the gut microbiota may have deleterious consequences for subsequent flavivirus infections.

SUBMITTER: Thackray LB

PROVIDER: S-EPMC5908250 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Oral Antibiotic Treatment of Mice Exacerbates the Disease Severity of Multiple Flavivirus Infections.

Thackray Larissa B LB Handley Scott A SA Gorman Matthew J MJ Poddar Subhajit S Bagadia Prachi P Briseño Carlos G CG Theisen Derek J DJ Tan Qing Q Hykes Barry L BL Lin Hueylie H Lucas Tiffany M TM Desai Chandni C Gordon Jeffrey I JI Murphy Kenneth M KM Virgin Herbert W HW Diamond Michael S MS

Cell reports 20180301 13

Although the outcome of flavivirus infection can vary from asymptomatic to lethal, environmental factors modulating disease severity are poorly defined. Here, we observed increased susceptibility of mice to severe West Nile (WNV), Dengue, and Zika virus infections after treatment with oral antibiotics (Abx) that depleted the gut microbiota. Abx treatment impaired the development of optimal T cell responses, with decreased levels of WNV-specific CD8<sup>+</sup> T cells associated with increased i ...[more]

PMID: 29590614

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Project description:IntroductionThere are suggestions that virus co-infections may influence the clinical outcome of respiratory virus illness. We performed a systematic review of the literature to summarise the evidence.MethodsMEDLINE, EMBASE, Ovid and WEB of Science databases, major organisation websites and reference lists of published studies were searched. The quality of studies was assessed using the STROBE tool (von Elm et al., 1) Individual study data was analyzed using odds ratios and 95% confidence intervals as a measure of association between exposure (co-infection), patient outcome and results summarised using forest plots and tablesResultsNineteen (19) studies from all over the world were identified and included in the review. Most of the studies 73.7% (14/19) recruited children ? 6 years old. Evidence on the role of co-infection in increasing disease severity was inconclusive. In five out of eight studies, co-infection significantly increased risk of admission to general ward (OR: 2.4, 95% CI: 1.3 - 4.4, p = 0.005; OR: 2.4, 95% CI: 1.1 - 7.7, P = 0.04; OR: 3.1, 95% CI: 2.0 - 5.1, p = <0.001; OR: 2.4, 95% CI: 1.7-3.4, p = <0.0001 and OR: 2.3, 95% CI: 1.1 - 5.1, p = 0.34), one found it did not (OR: 0.59, 95% CI: 0.4 - 0.9, p = 0.02) and the other 2 had insignificant results. Similarly on risk of admission to ICU, some studies found that co-infection significantly increased risk of admission to ICU (OR: 2.9, 95% CI: 1.4 - 5.9, p = 0.004 and OR: 3.0, 95% CI: 1.7 - 5.6, p = <0.0001), whereas others did not (OR: 0.18, 95% CI: 0.05 - 0.75, p = 0.02 and OR: 0.3, 95% CI: 0.2 - 0.6, p = <0.0001). There was no evidence for or against respiratory virus co-infections and risk of bronchiolitis or pneumonia.ConclusionThe influence of co-infections on severe viral respiratory disease is still unclear. The observed conflict in outcomes could be because they were conducted in different seasons and covered different years and periods. It could also be due to bias towards the null, especially in studies where only crude analysis was conducted. Future studies should employ stratified analysis.

Dataset Information

Oral Antibiotic Treatment of Mice Exacerbates the Disease Severity of Multiple Flavivirus Infections.

Publications

Oral Antibiotic Treatment of Mice Exacerbates the Disease Severity of Multiple Flavivirus Infections.

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