ADP-Ribosylation in Antiviral Innate Immune Response

Du, Qian; Miao, Ying; He, Wei; Zheng, Hui

doi:10.3390/pathogens12020303

Cited by 3 publications

(5 citation statements)

References 135 publications

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“…Addition, recognition, and removal of ADP-ribosylation has emerged as an important battleground between the host antiviral immune response and viruses. Although the molecular targets of ADP-ribosylation, and the mechanistic consequences of that ADP-ribosylation, are mostly uncharacterized, there is clear function of host PARPs in the antiviral immune response and a clear role of viral macrodomains in antagonizing the host immune response [ 17 , 58 , 59 , 60 , 61 ]. Our evolutionary and functional data suggest that an important consideration is the degree to which the ADP-ribosylhydrolase activity encoded by some macrodomains is conserved amongst host antiviral macroPARPs and is conserved amongst viral macrodomains.…”

Section: Discussionmentioning

confidence: 99%

Recurrent Loss of Macrodomain Activity in Host Immunity and Viral Proteins

2023

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Protein post-translational modifications (PTMs) are an important battleground in the evolutionary arms races that are waged between the host innate immune system and viruses. One such PTM, ADP-ribosylation, has recently emerged as an important mediator of host antiviral immunity. Important for the host–virus conflict over this PTM is the addition of ADP-ribose by PARP proteins and removal of ADP-ribose by macrodomain-containing proteins. Interestingly, several host proteins, known as macroPARPs, contain macrodomains as well as a PARP domain, and these proteins are both important for the host antiviral immune response and evolving under very strong positive (diversifying) evolutionary selection. In addition, several viruses, including alphaviruses and coronaviruses, encode one or more macrodomains. Despite the presence of the conserved macrodomain fold, the enzymatic activity of many of these proteins has not been characterized. Here, we perform evolutionary and functional analyses to characterize the activity of macroPARP and viral macrodomains. We trace the evolutionary history of macroPARPs in metazoans and show that PARP9 and PARP14 contain a single active macrodomain, whereas PARP15 contains none. Interestingly, we also reveal several independent losses of macrodomain enzymatic activity within mammalian PARP14, including in the bat, ungulate, and carnivore lineages. Similar to macroPARPs, coronaviruses contain up to three macrodomains, with only the first displaying catalytic activity. Intriguingly, we also reveal the recurrent loss of macrodomain activity within the alphavirus group of viruses, including enzymatic loss in insect-specific alphaviruses as well as independent enzymatic losses in two human-infecting viruses. Together, our evolutionary and functional data reveal an unexpected turnover in macrodomain activity in both host antiviral proteins and viral proteins.

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Section: Discussionmentioning

confidence: 99%

Recurrent Loss of Macrodomain Activity in Host Immunity and Viral Proteins

2023

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“…Even beyond the activation of the immune response through the PARylation of host proteins related to immune pathways, PARP has antiviral activity through its PARylation of viral proteins responsible for viral maintenance, such as the Epstein–Barr nuclear antigen 1 (EBNA1) in Epstein–Barr virus (EBV), LANA1 in KSHV, nonstructural proteins in Zika and Chikungunya (CHIKV) virus, and the nucleocapsid protein in coronaviruses [ 72 ]. Some of these modifications have been identified as inhibiting critical viral functions, suggesting that PARylation may function as an immune response [ 72 ]. However, it is beyond the scope of this review to provide a comprehensive overview of the role of PARylation as an antiviral part of the innate immune system.…”

Section: Viral Utilization Of Parylationmentioning

confidence: 99%

“…However, it is beyond the scope of this review to provide a comprehensive overview of the role of PARylation as an antiviral part of the innate immune system. For a more comprehensive overview of PARylation as an antiviral function, we suggest the work of Du et al [ 72 ].…”

Section: Viral Utilization Of Parylationmentioning

confidence: 99%

“…Herpes simplex virus type 1, or HSV-1, is characterized by chronic long-term infection of the peripheral nervous system, enabled by HSV-1 transportation through axons to neuronal ganglia, where the long-term infection is established through latent HSV-1 infection characterized by the expression of a limited set of viral genes to evade immune detection [ 72 , 73 , 74 ]. However, despite latent infection accounting for such a large portion of HSV-1 infection, HSV-1 lytic reactivation can occur due to various stress stimuli [ 75 ].…”

Section: Viral Utilization Of Parylationmentioning

confidence: 99%

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PARP1 as an Epigenetic Modulator: Implications for the Regulation of Host-Viral Dynamics

Sobotka,

Tempera

2024

Pathogens

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The principal understanding of the Poly(ADP-ribose) polymerase (PARP) regulation of genomes has been focused on its role in DNA repair; however, in the past few years, an additional role for PARPs and PARylation has emerged in regulating viral-host interactions. In particular, in the context of DNA virus infection, PARP1-mediated mechanisms of gene regulations, such as the involvement with cellular protein complexes responsible for the folding of the genome into the nucleus, the formation of chromatin loops connecting distant regulatory genomic regions, and other methods of transcriptional regulation, provide additional ways through which PARPs can modulate the function of both the host and the viral genomes during viral infection. In addition, potential viral amplification of the activity of PARPs on the host genome can contribute to the pathogenic effect of viral infection, such as viral-driven oncogenesis, opening the possibility that PARP inhibition may represent a potential therapeutic approach to target viral infection. This review will focus on the role of PARPs, particularly PARP1, in regulating the infection of DNA viruses.

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“…There are two known forms of ADP-ribosylation: Poly (ADP-ribosyl) ation and mono (ADP-ribosyl) ation, commonly referred to as PARylation and MARylation, respectively[ 120 , 121 ]. These modifications regulate a myriad of cellular processes, including DNA damage response, unfolded protein response, cell cycle progression, cell death, metabolism, and immune responses[ 122 - 125 ]. Enzymes in both mammals and microbes can attach, erase, or recognize ADP-ribosyl moieties of target proteins[ 126 ].…”

Section: Viral Factors Affecting Liver Failurementioning

confidence: 99%

Pathogenesis and clinical features of severe hepatitis E virus infection

Orosz,

Sárvári,

Dernovics

et al. 2024

World J Virol

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The hepatitis E virus (HEV), a member of the Hepeviridae family, is a small, non-enveloped icosahedral virus divided into eight distinct genotypes (HEV-1 to HEV-8). Only genotypes 1 to 4 are known to cause diseases in humans. Genotypes 1 and 2 commonly spread via fecal-oral transmission, often through the consumption of contaminated water. Genotypes 3 and 4 are known to infect pigs, deer, and wild boars, often transferring to humans through inadequately cooked meat. Acute hepatitis caused by HEV in healthy individuals is mostly asymptomatic or associated with minor symptoms, such as jaundice. However, in immunosuppressed individuals, the disease can progress to chronic hepatitis and even escalate to cirrhosis. For pregnant women, an HEV infection can cause fulminant liver failure, with a potential mortality rate of 25%. Mortality rates also rise amongst cirrhotic patients when they contract an acute HEV infection, which can even trigger acute-on-chronic liver failure if layered onto pre-existing chronic liver disease. As the prevalence of HEV infection continues to rise worldwide, highlighting the particular risks associated with severe HEV infection is of major medical interest. This text offers a brief summary of the characteristics of hepatitis developed by patient groups at an elevated risk of severe HEV infection.

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ADP-Ribosylation in Antiviral Innate Immune Response

Cited by 3 publications

References 135 publications

Recurrent Loss of Macrodomain Activity in Host Immunity and Viral Proteins

Recurrent Loss of Macrodomain Activity in Host Immunity and Viral Proteins

PARP1 as an Epigenetic Modulator: Implications for the Regulation of Host-Viral Dynamics

Pathogenesis and clinical features of severe hepatitis E virus infection

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