Oral antibiotic treatment exacerbates the disease severity of multiple flaviviruses

Although the outcome of infection by many medically important flaviviruses ranges from asymptomatic to lethal, little is known about the acquired factors that modulate disease severity. Here, we found that oral antibiotic treatment increased susceptibility of mice to lethal infection by three emerging viruses of global concern: West Nile virus (WNV), Dengue virus and Zika virus. The effect of antibiotics on outcome following WNV infection was durable after cessation of treatment and transferable to gnotobiotic mice, and occurred even after three days of treatment with ampicillin only. Antibiotic treatment reduced the number of WNV-specific CD8+ T cells but spared the neutralizing antibody response, consistent with increased WNV burden observed in the central nervous system late in infection. Our results identify a role for the mammalian microbiota in modulating host adaptive immunity during WNV infection, and suggest that even short courses of oral antibiotics can have deleterious consequences for patients with flavivirus infections.