The large plaque phenotype observed with MHV68.DHS is similar to what is observed following infection with MHV68 constitutively expressing (or over-expressing) the lytic transcription factor RTA [65] . Also similar to MHV68.DHS, these viruses replicate to near wild-type levels in the lung but establish latency at lower levels in the spleen. The constitutive RTA-expressing viruses have been found to efficiently traffic to the spleen but fail to be maintained at this site [66] . This attenuation has been ascribed to the viruses producing excessive amounts of the RTA-inducible lytic genes, creating an intracellular environment favoring immediate entry into the lytic cycle rather than entering latency. Thus, during an infection, an important role for muSOX may be to ensure that factors driving lytic replication are not overrepresented. While it is tempting to speculate a connection between the increased percentage of lytically infected 3T3 cells and the latency establishment defect in vivo with MHV68.DHS, at present the precise relationship between these observations remains unclear.