The Antiviral Activities of Poly-ADP-Ribose Polymerases

Figures

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  Figure 1. Direct antiviral activities of PARPs. PARP13 and PARP7 can induce exosome-mediated degradation of target viral RNAs (1). PARPs can also inhibit viral genome replication. PARP12 inhibits viral RNA transcription within the cell cytoplasm (2). PARP1 or PARP5 PARylate or directly interact with EBNA1, preventing EBNA1 binding to the OriP promoter and inhibiting Epstein–Barr virus (EBV) replication (3). PARPs directly interact with viral proteins. PARP9/DTX3L complex and PARP12 catalyze mono-ADP-ribosylation (MARylation) of viral proteins leading to their proteosomal degradation while PARP10, through binding to avian influenza virus NS1, prevents viral RNA replication. PARP13 binds already PARylated influenza A virus proteins leading to their proteosomal degradation (4). Finally, PARP7, -10, -12 and -13 are inhibitors of viral translation stopping the formation of the translation initiation complex on viral mRNA (5).

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  Figure 2. Indirect antiviral activities of PARPs through immunomodulation. PARP1 and PARP11-induced MARylation of the β-transducin repeat-containing protein (β-TrCP), an E3 ubiquitin ligase, promotes interferon alpha/beta receptor 1 (IFNAR1) ubiquitination and degradation (1). Concerning RNA virus sensing pathways, PARP13 overexpression enhances oligomerization of retinoic acid-inducible gene I (RIG-I) (2), which leads to robust activation of downstream antiviral signaling through the interferon regulatory factor 3 (IRF3) pathway. On the other hand, PARPs can also downregulate the antiviral defenses. PARP7 MARylates TANK-binding kinase 1 (TBK1), decreasing IRF3 activation and leading to impaired IFN production (3). Otherwise, PARP12 enhances the signaling cascade, leading to NF-κB activation, whereas PARP10 exerts negative feedback on this pathway through MARylation of NF-κB essential modulator (NEMO) (4). PARP13 mediates the degradation of several host IFN mRNAs (5), thereby acting as a negative feedback regulator of the interferon response. The PARP9–DTX3L complex is a direct binding partner of STAT-1, promoting STAT-1 phosphorylation and nuclear relocalization, thereby increasing ISG…