Viral microRNAs EBV and KSHV exploit microRNAs to modulate both viral and cellular processes

Abstract

MiRNAs are a class of small regulatory RNAs that have been shown to be utilized by plants and mammals as well as viruses. Via binding to the 3’ UTR of target mRNA microRNAs can specifically induce degradation or translational inhibition. Gammaherpesviruses encode the most viral miRNAs, with 25 pre-miRNAs for EBV and 12 for KSHV, the latter being the best characterized at the moment. Viral miRNAs can target both cellular and viral transcripts. The viruses exploit miRNAs to optimize the cellular environment for infection and replication; miRNAs have been shown to play a role in maintaining the latent stage and modulating the host immune response. Viral microRNAs are thought not to be necessary for infection but are involved in protecting the infected cell. Viral targets include the EBV DNA polymerase BALF5 to prevent accidental induction of viral replication and the viral proteins LMP1 and -2a to promote cell survival and evasion of the immune system and the RTA latent-lytic switch of KSHV. Cellular miRNA targets include MICB, which plays a role in immune recognition of infected cells (EBV & KSHV), and IκBα, the ‘brake’ on the NFκB pathway (KSHV). Homology to cellular microRNAs is an additional method that viruses use to exploit the miRNA system.