The Zinc Finger Antiviral Protein ZAP Restricts Human Cytomegalovirus and Selectively Binds and Destabilizes Viral <i>UL4</i> / <i>UL5</i> Transcripts
Ana Cristina Gonzalez-Perez, Markus Stempel, Emanuel Wyler, Christian Urban, Antonio Piras, Thomas Hennig, Sabina Ganskih, Yuanjie Wei, Albert Heim, Markus Landthaler, Andreas Pichlmair, Lars Dölken, Mathias Munschauer, Florian Erhard, Melanie M. Brinkmann
Abstract
Viral infections have a large impact on society, leading to major human and economic losses and even global instability. So far, many viral infections, including human cytomegalovirus (HCMV) infection, are treated with a small repertoire of drugs, often accompanied by the occurrence of resistant mutants. There is no licensed HCMV vaccine in sight to protect those most at risk, particularly immunocompromised individuals or pregnant women who might otherwise transmit the virus to the fetus. Thus, the identification of novel intervention strategies is urgently required. In this study, we show that ZAP decelerates the viral gene expression cascade, presumably by selectively handpicking a distinct set of viral transcripts for degradation. Our study illustrates the potent role of ZAP as an HCMV restriction factor and sheds light on a possible role for UL4 and/or UL5 early during infection, paving a new avenue for the exploration of potential targets for novel therapies.