Enhanced replication of mouse adenovirus type 1 following virus-induced degradation of protein kinase R (PKR)

Danielle E. Goodman; Carla D. Pretto; Tomas A. Krepostman; Kelly E. Carnahan; Katherine R. Spindler

We examined PKR protein levels during MAV-1 infection and found that PKR was 333 depleted from the cells as early as 12 hpi (Fig. 7) . Depletion was seen in a wide variety of cell 334 types, including immortalized C57BL/6 MEFs, primary C57BL/6 peritoneal macrophages, and 335 CMT93 mouse colon carcinoma cells. Once depleted, PKR protein levels never returned to mock 336 infected PKR protein levels during infection. Activation (transautophosphorylation) of PKR (6-337 9) was not required for this depletion, because kinase-dead mouse PKR was also depleted from 338 The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It . https://doi.org/10.1101/584680 doi: bioRxiv preprint macrophages during MAV-1 infection (Fig. 3) , times when the PKR protein levels were depleted 345 ( Fig. 2A) . While PKR mRNAs in C57BL/6 MEFs were depleted 33% at 48 hpi and 40% at 72 346 hpi compared to mock lysates, this is not sufficient to explain the 84% and 94% reduction, 347 respectively, in PKR protein levels at those time points (Fig. 2B ). More likely, the reduction in 348 The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It . https://doi.org/10.1101/584680 doi: bioRxiv preprint