UC San Diego

Kaposi’s sarcoma-associated herpesvirus (KSHV) is the etiological agent of Kaposi’s sarcoma, an AIDS-related endothelial malignancy. In an infected cell population, KSHV largely exists as a latent episome, while a small percentage of latent virus undergoes lytic reactivation. The latent-to-lytic switch of KSHV is pathologically important, tightly regulated event that involves extensive host-virus crosstalk. Long non-coding RNAs (lncRNAs) are a diverse class of RNA regulators that have been shown to involve in the life cycles of many different viruses. However, the roles of lncRNAs in KSHV lytic reactivation have been unexplored. This study utilizes two cellular models of KSHV latent infection of different tissue origins to uncover differentially expressed lncRNAs during KSHV lytic reactivation via RNA-seq, revealing lncRNAs that may function in modulating virus lytic replication. Using CRISPR interference (CRISPRi), one of the novel differentially expressed lncRNAs, AC017002.3, was found to positively regulate KSHV early lytic transcript level. Since lncRNAs tend to function in ribonucleoprotein complexes, to address the mechanism by which AC017002.3 functions, RNA affinity pull-down was performed to search for its potential interacting proteins. hnRNP K and ILF2 were found to associate with AC017002.3. While functional validation of possible ribonucleoproteins involving AC017002.3 need to be conducted, this study provides the first evidence that host lncRNAs regulate KSHV lytic reactivation.