Intracellular mono-ADP-ribosyltransferases at the host–virus interphase

Abstract

The innate immune system, the primary defense mechanism of higher organisms against pathogens including viruses, senses pathogen-associated molecular patterns (PAMPs). In response to PAMPs, interferons (IFNs) are produced, allowing the host to react swiftly to viral infection. In turn the expression of IFN-stimulated genes (ISGs) is induced. Their products disseminate the antiviral response. Among the ISGs conserved in many species are those encoding mono-ADP-ribosyltransferases (mono-ARTs). This prompts the question whether, and if so how, mono-ADP-ribosylation affects viral propagation. Emerging evidence demonstrates that some mono-ADP-ribosyltransferases function as PAMP receptors and modify both host and viral proteins relevant for viral replication. Support for mono-ADP-ribosylation in virus–host interaction stems from the findings that some viruses encode mono-ADP-ribosylhydrolases, which antagonize cellular mono-ARTs. We summarize and discuss the evidence linking mono-ADP-ribosylation and the enzymes relevant to catalyze this reversible modification with the innate immune response as part of the arms race between host and viruses.

Mono-ADP-ribosylation by PARP10 inhibits Chikungunya virus nsP2 proteolytic activity and viral replication

“…HEK293 cells were transfected with siRNA oligo pools targeting the IFNα-inducible PARP10, PARP12, PARP14, and PARP15 (Supplementary Fig. 1a, b and [ 6 , 14 , 52 ]), prior to transfection with CHIKV replicon RNA. This replicon encodes the four non-structural proteins but lacks the open reading frame for the structural proteins.…”

“…It has been associated with DNA damage repair, gene expression, signaling, stress response and cell death [ 1 , 25 ]. Recent findings indicate a role for MARylation in host–pathogen conflicts [ 1 , 14 , 25 ]. The expression of several MARylating PARPs is triggered by type I interferons (IFNs) or pathogen-associated molecular patterns (PAMPs), such as LPS, as part of an innate immune response to pathogens [ 6 , 8 , 11 , 14 , 26 – 29 ].…”

Emerging Role of Nicotinamide Riboside in Health and Diseases

“…Furthermore, the upregulations of PARP genes and NAD + biosynthetic gene nampt were observed in SARS-CoV-2 infected individuals [ 23 , 106 ]. PARPs play key roles in antiviral immune response [ 107 ]. The induction of PARPs that are known to use NAD + as the co-substrate to catalyze mono-ADP-ribosylation (MARylation) further decreased the cellular NAD + contents.…”

ADP-Ribosylation in Antiviral Innate Immune Response

“…Therefore, PARP13 is the only PARP family member with a catalytically inactive domain [ 12 , 13 ]. In fact, only PARP1, 2, 3, TNKS1 and TNKS2 retain these residues and catalytic PARylation [ 14 ], while the rest of PARPs (except PARP13) possess the MARylation activity due to the substitution of the Glu residue [ 8 , 15 , 16 ]. In brief, the ability of PARPs to catalyze MARylation or PARylation of their protein substrates depends on conserved structural features such as the catalytic triad and the presence of certain cofactors.…”

“…During this last decade, several studies uncovered the roles of ADP-ribosylation in antiviral immunity [ 31 , 32 ]. Of note is that there are many PARPs that perform antiviral functions without their catalytic activity, and will not be discussed in detail here [ 15 ]. In this review, we mainly summarize and discuss new findings on the role of ADP-ribosylation occurred on the host and viral proteins in antiviral response.…”