As PEL is etiologically associated with infection with oncogenic γ-herpesviruses, decreased ERK and Akt activation reduces viral gene expression and viral loads in PEL cells [37, 38, 58]; thus, selective RNF5 inhibition suppresses KSHV lytic gene expression and lytic replication, consequently attenuating or eliminating genomic viral DNA loads and persistent KSHV infection (Figs 6 and 7). This evidence concerns the gene RNF5 and infection.