**5. Evidence of abortive lytic cycle and their role in tumorigenesis**

In the absence of other lytic genes, particularly those encoding late structural proteins, without the formation of infective viral particles, BZLF1 expression is termed the "abortive lytic cycle" (**Figure 4**) [13]. The existence of abortive cycles was demonstrated in EBV-associated malignancies through the detection of either the ZEBRA protein (via monoclonal antibodies) or mRNA: Hodgkin disease [17], Non-Hodgkin lymphoma (NHL) [18, 88], NPC [20], or Burkitt lymphoma [21]. Decades ago, we revealed the early stages of EBV replication in lymphomas in scid/hu mice, assessed by the expression of ZEBRA expression, whereas the VCA expression late replicate protein proved to be weak [89]. In a recent review, the authors discussed evidence supporting an abortive lytic cycle with several lytic genes expressed, such as immunomodulatory (BCRF1, BARF1, BNLF2A, BGLF5, and BILF1) and anti-apoptotic (BHRF1 and BALF1) proteins. In their paper, the authors also discussed how the EBV immunomodulatory mechanisms result in paracrine signals that feed tumor cells. The existence of such abortive lytic cycles would reconcile the requirement of lytic expression in view of viral tumorigenesis without relying on a complete cycle that would induce cell lysis, thus releasing the newly formed infective viral particles [13].

### **Figure 4.**

*The existence of abortive lytic cycles (presence of ZEBRA protein, with absence of other lytic genes, particularly those encoding late structural proteins) would reconcile the requirement of lytic expression in view of viral tumorigenesis without relying on a complete lytic (from Ref. [13] with permission).*
