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

Andrew J. McNamara; Pranav Danthi

The loss of the IKK complex components prevents nuclear translocation and 32 phosphorylation of NF-κB, thereby preventing gene expression. Our studies 33 demonstrate that reovirus infection selectively blocks NF-κB, likely to counteract its 34 antiviral effects and promote efficient viral replication. The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It . https://doi.org/10.1101/843680 doi: bioRxiv preprint 3 important for the cell to mediate this response. In this study, we show that in cells 40 infected with mammalian reovirus, NF-κB is inactive. Further, we demonstrate that NF-41 κB is rendered inactive because virus infection results in reduced levels of upstream 42 intermediaries (called IKKs) that are needed for NF-κB function. Based on previous 43 evidence that active NF-κB limits reovirus infection, we conclude that inactivating NF-κB 44 is a viral strategy to produce a cellular environment that is favorable for virus replication. 45 . CC-BY 4.0 International license is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It . https://doi.org/10.1101/843680 doi: bioRxiv preprint