Flu virus susceptibility of ago 1 / 3 double null mice Enhanced Susceptibility to Influenza A Virus of Ago 1 / 3 1 Double Null Mice

22 RNAi is a critical component of many cellular anti-viral responses in plants, 23 invertebrates, and mammals. However, its in vivo role in host protection from the 24 negative sense RNA virus Influenza Type A is unclear. Here we have examined the role 25 of RNAi in host defense to flu by analyzing Argonaute 1 and 3 double knock out mice, 26 deficient in components of the RNA induced silencing complex. Compared to littermate 27 controls, flu-infected double knock out mice exhibited increased mortality, consistent with 28 more severe alveolitis and pneumonitis. These data indicate that optimal resistance to 29 flu requires Argonaute 1 and/or 3. Enhanced mortality of double knock out mice was 30 associated neither with increased viral replication nor with differential pulmonary 31 recruitment or function of innate and adaptive immune cells. Given the absence of 32 detectable immune defects, our results support the notion that the enhanced flu 33 susceptibility of DKO mice arises from an intrinsic impairment in the ability of lung cells 34 to tolerate flu-elicited inflammation. 35 36 on A uust 5, 2017 by gest http/jvi.asm .rg/ D ow nladed fom Flu virus susceptibility of ago1/3 double null mice