STAT3 and STAT6 have been reported to activate Ire1α arm of UPR and viral infection may trigger UPR by inducing ER stress or even by engaging the PRRs.18 Therefore, we next investigated whether KSHV could activate UPR in infected macrophages and found that the expression of Ire1α and its target XBP1s as well as ATF4 increased, suggesting that Ire1α and PERK branches of UPR were activated. Here, ATF4 is linked to viral infectious disease.