In this study, transfection of cells with egr-1/pCDNA3.1(+) resulted in a significant increase in virus-encoded ORF50 transcription followed by the expression of early-lytic ORF59 protein and late-lytic gene (ORF8) encoding gB (Fig. 4B, C) ; all of which are indicators of an active lytic replication of KSHV [12, 28, 29] . MAPK signaling was observed to regulate Egr-1 expression in cells transfected with egr-1/pCDNA3.1(+) (Fig. 4D) . Interestingly, treatment of KSHV-infected cells with TPA induces a lytic replication via MAPK signaling [12, 13] . In addition, Egr-1 is a downstream target of Raf/MEK/ERK signaling (Fig. 4D ) [6, 30] . It is unclear at this time if the effect of egr-1/pcDNA3.1 over-expression resembles the milieu supporting a lytic infection in vivo. It is important to remember that KSHV reactivation can be regulated by other cellular factors including STAT6, NFkB, and XBP-1 [31, 32, 33] . Thus, activation of a lytic infection may require unique cellular factors under specific conditions or a combination of factors. Further investigation is required to unravel the environment(s) supporting virus reactivation under physiologically relevant conditions; especially in terms of the different transcription factors.