Host shutoff manifests with delayed early kinetics during lytic replication, consistent with the onset of muSOX expression [16] . We therefore hypothesized that MHV68.DHS would be attenuated during lytic viral replication in the lung. We infected C57BL/ 6 mice intranasally with 5610 4 pfu of MHV68.WT, MHV68.DHS, or MHV68.MR, and monitored viral titers in the lung at 3, 5, and 7 dpi by plaque assay. Viral titers were equivalent at 3 dpi for all three viruses, and at 5 and 7 dpi we observed only a very modest 2-3 fold defect in MHV68.DHS relative to MHV68.MR accumulation ( Figure 6 ). Although MHV68.WT reached higher titers than MHV68.MR at 5 dpi, the two viruses accumulated to equivalent levels at all earlier and later timepoints (see subsequent sections). To ensure MHV68.DHS had not reverted back to WT or incorporated any compensatory mutations, we sequenced the muSOX gene from infected lung homogenate but found no changes. Thus, contrary to our hypothesis, host shutoff appears largely dispensable for acute replication of gammaherpesviruses in vivo.