Loss of IKK subunits limits NF-?B signaling in reovirus infected cells

Andrew J. McNamara; Pranav Danthi

Shigella, an intracellular pathogenic bacteria secretes an effector with E3 ligase activity 261 which targets NEMO for proteasomal degradation (32). In addition to degradation, 262 pathogens also sequester the IKK complex (IAV NS1 protein) or prevent its activation 263 (HCMV, enterovirus)(33-35). Here we show that reovirus infection leads to the loss of 264 both IKKβ and NEMO (Fig. 4) . This loss was not due to differences in the steady state 265 levels of IKKβ mRNA in reovirus infected cells (not shown). It was also independent of 266 the effect of reovirus infection on host translation suggesting that IKKβ levels were 267 controlled post translationally (not shown). Reovirus does not encode a protease, ruling 268 out a direct effect of a viral protease on IKKβ. Preventing acid-dependent protease 269 suggesting that certain mouse cell types do not require NF-κB for IFN production (37, 281 38), we found in our RNA-seq analyses that inhibition of NF-κB did not affect IFN 282 production ( Fig. 1) . Thus the antiviral effect of NF-κB is independent from IFN. In 283 contrast with IFN, we found that the expression of several other chemokines and 284 cytokines was inhibited in reovirus infected cells. We hypothesize that one or more of 285 these factors negatively regulates reovirus replication. 286