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

The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/248617 doi: bioRxiv preprint Next, we examined if aminoglycoside-mediated induction of antiviral immunity was specific 170 to the vaginal tract or if similar protection could be observed in other mucosal surfaces 171 such as the respiratory tract. A single intranasal dose of neomycin sufficed to significantly 172 upregulate ISG expression in the lung (Fig. 3a) . To determine if this ISG induction results 173 in host antiviral resistance, we tested neomycin-mediated protection in a functionally 174 relevant mouse model of influenza infection. Many inbred mouse strains, including 175 C57BL/6, lack Mx1 (Ref. 13 ). Mx1 encodes the myxovirus resistance protein 1, a dynamin-176 like GTPase that blocks primary transcription of influenza by binding to viral nucleoproteins 177 14-17 . Mx1 is an ISG that is induced by neomycin treatment (Fig. 3a) , and when expressed, 178 confers resistance to influenza A virus in mice 14 . In mice lacking Mx1 such as C57BL/6 179 strains, innate resistance to influenza is abrogated, and they rely on adaptive immunity. 180