Prazoles Targeting Tsg101 Inhibit Release of Epstein-Barr Virus following Reactivation from Latency
Sai Sudha Mannemuddhu, Huanzhou Xu, Christopher K. E. Bleck, Nico Tjandra, Carol Carter, Sumita Bhaduri‐McIntosh
Abstract
Production of virions is necessary for the ubiquitous Epstein-Barr virus (EBV) to persist in humans and can set the stage for development of EBV cancers in at-risk individuals. In our attempts to identify inhibitors of the EBV lytic phase, we previously found that a prazole proton pump inhibitor, known to block the interaction of ubiquitin with the ESCRT-1 factor Tsg101, blocks production of EBV. We now find that three structurally distinct prazoles impair maturation of EBV capsids and virion transport from the nucleus and, by interfering with Tsg101, prevent EBV release from lytically active cells. Our findings not only implicate Tsg101 in EBV production but also identify widely used prazoles as candidates to prevent development of posttransplant EBV lymphomas.