Microbiota-independent antiviral protection conferred by aminoglycoside antibiotics

Smita Gopinath; Myoungjoo V. Kim; Tasfia Rakib; Patrick W. Wong; Michael van Zandt; Natasha A. Barry; Tsuneyasu Kaisho; Andrew L. Goodman; Akiko Iwasaki

b. Mice treated subcutaneously with Depo-Provera were inoculated intravaginally with the indicated aminoglycoside (1mg) or PBS daily for 1 week. After 1 week of treatment, mice were infected with HSV-2. Viral titers in the vagina were measured at indicated time points (a-c). Viral titers in the dorsal root ganglion were measured 4 days post infection (d). Error bars represent SEM and signi cance was calculated using unpaired t-tests. Exact p values are reported in Table S2 . Depo-treated outbred germ-free swiss-webster mice (n=4-5) were treated with 1mg neomycin or PBS daily for 6 days and vaginal gene expression analyzed. Error bars represent SEM and statistical signi cance was determined using a one-way ANOVA with * representing p values < 0.05. Exact p values are reported in Table S2 . Mice treated subcutaneously with Depo-Provera were inoculated intravaginally with neomycin (1mg or 4.5 mgs) or PBS for 1 day (n = 3-5 mice per group). 24 hours later, vaginal gene expression was quanti ed. Depo-treated mice were innoculated intravaginally with neomycin (1mg/day) or PBS daily for 6 days. Mice were sacri ced 1,3 and 7 days after the last neomycin treatment as shown in (b) and vaginal gene expression analyzed at each time point (c). Depo-treated mice were inncoluated with 1mg neomycin daily for 6 days and vaginal and lung ISG expression analyzed in mice 1 day post neomycin treatment (d). Error bars represent SEM and signi cance was calculated using unpaired t-tests, corrected for multiple comparison. Exact p values are reported in Table S2 . Mice were treated subcutaneously with Depo-Provera and ve days after treatment were inoculated intravaginally with the indicated antibiotics (1mg/day) for 2 days (n=3 mice per group). Vaginal gene expression (a,b) and mitochondrial DNA abundance (c) was analyzed via qPCR . Signi cance was calculated using unpaired t-tests, correcting for multiple comparisons with * indicating p values <0.05. Exact p values for all comparisons are reported in Table S2 .