IFI16 Partners with KAP1 to Maintain Epstein-Barr Virus Latency
Huanzhou Xu, Xiaofan Li, Beth A. Rousseau, Ibukun A. Akinyemi, Tiffany R. Frey, Kevin Zheng Zhou, Lauren E. Droske, Jennifer A. Mitchell, Michael T. McIntosh, Sumita Bhaduri‐McIntosh
Abstract
The interferon-gamma inducible protein 16 (IFI16) is a nuclear DNA sensor that mediates antiviral responses by activating the inflammasome, triggering an interferon response, and silencing lytic genes of herpesviruses. The last, which helps maintain latency of the oncoherpesvirus Epstein-Barr virus (EBV), is accomplished via H3K9me3 heterochromatinization through unknown mechanisms. Here, we report that IFI16 physically partners with the core constitutive heterochromatin machinery to silence the key EBV lytic switch protein, thereby ensuring continued viral latency in B lymphocytes. We also find that disruption of latency involves rapid transcriptional downregulation of IFI16. These findings point to hitherto unknown physical and functional partnerships between a well-known antiviral mechanism and the core components of the constitutive heterochromatin machinery.