Downregulation of IRF4 induces lytic reactivation of KSHV in primary effusion lymphoma cells

Primary effusion lymphoma (PEL), associated with the latent infection by KSHV, constitutively expresses interferon-regulatory factor 4 (IRF4). We recently showed that IRF4 differentially regulates expression of cellular interferon-stimulated genes (ISGs) and viral genes (Forero et al., 2013). Here, using inducible IRF4 knockdown, we demonstrate that IRF4 silencing results in enhanced transcription of KSHV replication transactivator RTA. As a result viral transcription is increased leading to virus reactivation. Taken together, our results show that IRF4 helps maintain the balance between latency and KSHV reactivation in PEL cells.