Novel small non-coding RNAs of Epstein-Barr virus upregulated upon lytic reactivation aids in viral genomic replication and virion production

Epstein-Barr virus (EBV) employs various strategies for long-term survival, including the expression of non-coding RNAs (ncRNAs). This study uncovers and characterizes two novel EBV-encoded ncRNAs, p7 and p8, which are upregulated during lytic reactivation and interact with both viral and host genomes. These ncRNAs bind to cellular RNA transcripts, significantly reducing ARMCX3 mRNA levels, with p8 also influencing PTPN6 and RPL24 expression. Both p7 and p8 downregulate LMP1 expression, even though p7 does not directly bind to LMP1 RNA. Furthermore, these ncRNAs interact with the OriLyt region, promoting viral DNA replication. Functional assays indicate that p7 and p8 enhance cell proliferation and inhibit apoptosis by modulating the p53 pathway and suppressing pro-apoptotic proteins. These findings highlight the role of p7 and p8 in supporting EBV persistence by regulating viral replication, cell survival, and immune evasion, making them promising targets for therapeutic strategies in EBV-related diseases.