PARP14: A key ADP-ribosylating protein in host-virus interactions?

Over 300 posttranslational modifications (PTMs) are known to modify the functions of proteins by affecting processes ranging from activation, degradation, localization, secretion, recognition, and regulation [1]. One such PTM, ADP-ribosylation, can be defined as the transfer of a single ADP-ribose (Mono-ADP-ribosylation (MAR)) or multiple ADP-ribose (Poly-ADPribosylation (PAR)) units to target proteins utilizing nicotinamide adenine dinucleotide (NAD+) as the substrate. PARP14 is a MARylating enzyme that is implicated in a range of processes from tumorigenesis to DNA repair. Most notably, PARP14 is well known in the literature for promoting the anti-inflammatory interleukin (IL)-4-mediated signaling pathway by activating STAT6-dependent gene expression and inhibiting STAT-1-dependent gene expression. However, PARP14 expression is also induced by interferon (IFN), and it enhances host IFN responses to lipopolysaccharide (LPS), poly(I:C), and viral infection, indicating a role for PARP14 in restricting viral and bacterial infections. Despite these results, data supporting a significant role for PARP14 in the antiviral response are limited. More studies are needed to identify specific roles for PARP14 during viral infections, determine its targets following infection, and elucidate the mechanisms by which PARP14 modulates inflammatory pathways.