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.

Full text access

Thackray LB, Handley SA, Gorman MJ, Poddar S, Bagadia P, Briseño CG, Theisen DJ, Tan Q, Hykes BL Jr., Lin H, Lucas TM, Desai C, Gordon JI, Murphy KM, Virgin HW, Diamond MS. Cell Rep. 2018 Mar 27;22(13):3440-3453.e6. doi: 10.1016/j.celrep.2018.03.001. PubMed PMID: 29590614.

Keywords: Dengue virus; West Nile virus; Zika virus; flavivirus; gut microbiota; Oral Antibiotic Treatment of Mice Exacerbates the Disease Severity of Multiple Flavivirus Infections; immunity; oral antibiotics; pathogenesis determinants; risk factors.

Join for free INPST as a member

The International Natural Product Sciences Taskforce (INPST) maintains up-to-date lists with conferences, grants and funding opportunities, jobs and open positions, and journal special issues with relevance for the area of phytochemistry and food chemistry, pharmacology, pharmacognosy research, and natural product science.

Apply for the INPST 2018 Science Communication Award (Gold: 2000 USD / Silver: 1000 USD / Bronze: 500 USD)