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The zinc finger antiviral protein ZAP destabilises viral transcripts and restricts human cytomegalovirus

Item Type:Preprint
Title:The zinc finger antiviral protein ZAP destabilises viral transcripts and restricts human cytomegalovirus
Creators Name:Gonzalez-Perez, A.C. and Stempel, M. and Wyler, E. and Urban, C. and Piras, A. and Hennig, T. and Heim, A. and Landthaler, M. and Pichlmair, A. and Erhard, F. and Dölken, L. and Brinkmann, M.M.
Abstract:Interferon-stimulated gene products (ISGs) play a crucial role in early infection control. The ISG zinc finger CCCH-type antiviral protein 1 (ZAP/ZC3HAV1) antagonises several RNA viruses by binding to CG-rich RNA sequences, whereas its effect on DNA viruses is largely unknown. Here, we decipher the role of ZAP in the context of human cytomegalovirus (HCMV) infection, a β-herpesvirus that is associated with high morbidity in immunosuppressed individuals and newborns. We show that expression of the two major isoforms of ZAP, the long (ZAP-L) and short (ZAP-S), is induced during HCMV infection and that both negatively affect HCMV replication. Transcriptome and proteome analyses demonstrated that the expression of ZAP decelerates the progression of HCMV infection. SLAM-sequencing revealed that ZAP restricts HCMV at early stages of infection by destabilising a distinct subset of viral transcripts with low CG content. In summary, this report provides evidence of an important antiviral role for ZAP in host defense against HCMV infection and highlights its differentiated function during DNA virus infection.
Keywords:ZAP, ZC3HAV1, ISG, Antiviral, DNA Virus, Herpesvirus, HCMV, Innate Immunity, Animals, Mice
Source:bioRxiv
Publisher:Cold Spring Harbor Laboratory Press
Article Number:2020.09.15.297804
Date:17 September 2020
Official Publication:https://doi.org/10.1101/2020.09.15.297804

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