RNAs in Epstein–Barr virions control early steps of infection

Abstract

Herpesviruses are dsDNA viruses, but their virions may additionally contain RNAs that can be transduced to recipient cells. The biological functions of herpes virion RNA species are unknown. Here we address this issue for EBV, a widespread human herpesvirus with oncogenic potential. We show that EBV-derived particles that include virions, virus-like particles, and subviral vesicles contain viral mRNAs, microRNAs, and other noncoding RNAs. Viral RNAs were transduced during infection and deployed immediate functions that enhanced EBV's capacity to transform primary B cells. Among these transduced viral RNAs, BZLF1 transcripts transactivated viral promoters triggering the prelatent phase of EBV infection, noncoding EBV-encoded RNA transcripts induced cellular cytokine synthesis, and BNLF2a mRNA led to immune evasion that prevented T-cell responses to newly infected B cells. Hence, transduced viral RNAs govern critical processes immediately after infection of B cells with EBV and likely play important roles in herpesviral infection in general.