This effect can be due to the mixture of functions governed by XBP-1, related in addition to its effect on ER physiology also to its role in modulating the interferon response and other signaling pathways, more relevant for immune cells. Indeed, measurements of the IFNb levels were reduced in the XBP-1 KO cells. While this may have Azlocillin sodium salt limited importance to viral propagation in fibroblasts, it may promote the infection in macrophages, leading to robust induction of the anti-viral state thus allowing better viral clearance. Further support for the role of XBP-1 in MCMV infection comes from the in vivo studies. We used two approaches. In one we ubiquitously removed XBP-1 before infection and in the second we used Cre-expressing viruses to remove XBP-1 only in infected cells, an approach that was previously used to demonstrate the role of Blimp1 for MHV-68 infection and to monitor viral dissemination in vivo. Both models yielded a similar effect for XBP-1 deletion. The effect was more robust than what was measured for fibroblasts, indicating that in vivo, XBP-1 probably plays a more central role for MCMV acute infection. The importance of XBP-1 at low MOI and its pronounced effect in vivo suggest that under MCMV reactivation from latency, conditions in which viral dosage is minimal, XBP-1 should display an even larger significance. In conclusion, our study reveals the multifaceted importance of the IRE1/XBP-1 pathway for MCMV infection. It is likely that the manipulation of this pathway by cytomegaloviruses is related to the immunological roles of the UPR rather than to its role in ER quality control. Our data show that while at the early stages of infection IRE1 is Bay 11-7085 important by executing XBP-1 splicing, at later times when the cells are committed to viral protein synthesis and generation of viral progeny, IRE1 becomes toxic and the virus targets it for degradation. The exact activities of IRE1 that MCMV and HCMV evolved to avoid at the late phases of infection remain to be elucidated. Understanding the spatial and cellular specific roles of the UPR in the context of infection may allow the design of therapies that may be effective also in immunocompromised patients, severely affected by this pathogen. Colorectal cancer has the third highest incidence and mortality rate among the US population.