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Recently, Dr.
Zhu Huifang from the First Affiliated Hospital of Gannan Medical College was invited to publish a review paper titled: When PARPs Meet Antiviral Innate Immunity in Trends in Microbiology.
The role of virus in natural immunity and its molecular mechanism
.
This article focuses on the regulatory functions of PAPRs family members in the antiviral innate immune signal pathway
.
Innate immunity is the first line of defense against virus immunity, and it plays an important role in the control of virus infection and replication
.
The classic antiviral innate immunity is the release of Type I interferon (IFN-I) mediated by pattern-recognition receptors (PRRs) and the downstream JAK-STAT (Janus kinase-signal transducer and activation of The transcription signal pathway induces the production of a large number of Interferon-stimulated genes (ISGs)
.
Poly (ADP-ribose) polymerase PARPs (Poly (ADP-ribose) polymerase) are a superfamily of multifunctional protein post-translational modification enzymes that exist in most eukaryotes.
They are responsible for the transfer of ADP-ribose groups to the target.
Proteins and target proteins are modified by ADP ribosylation (ADPr), which is widely involved in important biological processes such as DNA damage repair, transcription regulation, and chromosomal protein remodeling
.
In mammals, a total of 17 PARP family members have been found, named PARP1-16.
Among them, PARP5 has two subtypes, PARP5a and PARP5b
.
Recent studies have shown that PARPs not only play an irreplaceable role in maintaining genome stability and regulating signal pathways, but also play an important regulatory role in antiviral natural immunity
.
Figure 1.
The members of the PARPs family regulate the antiviral innate immune signal pathway PARP13, also known as ZAP (zinc-fingerantiviral protein), which is one of the PARPs family members with antiviral functions that have been studied in depth
.
ZAP can not only directly bind RNA virus genome and mRNA and mediate their degradation, thereby inhibiting virus replication, but also can promote RIG-I oligomerization by binding to pattern recognition receptor RIG-I (Retinoicacidinducible gene-I).
Polymerization, thereby enhancing the signal transmission function of RIG-I and mediating the production of IFN-I
.
In addition, some PARPs, such as PARP9, also have regulatory effects on the JAK-STAT signaling pathway
.
PARP9 interacts with the E3 ubiquitin ligase DTX3L (E3 ubiquitin ligase Deltex E3 ubiquitin ligase 3L) and forms a complex to further promote the nuclear entry of STAT1 and the transcriptional regulation of ISGs
.
Figure 2.
Direct antiviral effects of PARPs family members and immune escape strategies of viruses In addition to promoting the host's antiviral natural immune response, some members of the PARPs family also assist the virus to complete immune escape
.
PARP11 can promote the degradation of type I interferon receptor (IFN-α/β receptor, IFNAR) by the proteasome pathway; under normal physiological functions, PARP1 is usually located in the nucleus, while facing the influenza A virus (Influenza Avirus, During IAV infection, hemagglutinin (HA) expressed by IAV can bring PARP1 from the nucleus to the cytoplasm and further induce the degradation of IFNAR
.
In addition, Coronavirus (CoV) can antagonize the antiviral function of PARP12 and PARP14 by expressing viral proteins containing conserved macrodomain domains, and achieve the effect of immune escape
.
Currently known PARPs involved in antiviral innate immune regulation mainly have a limiting effect on RNA viruses, but little is known about the innate immune regulation function in response to DNA virus infection; in addition, the pattern recognition receptors involved are also very limited.
So far, it has only been found to have a regulatory function on the innate immune response mediated by RIG-I
.
Therefore, in future research work, it may be possible to explore the role of PARPs in anti-DNA virus innate immunity and other pattern recognition receptor types, such as TLRs (Toll-like receptors) or DNA receptors such as cGAS-STING.
The function of the innate immune signaling pathway
.
PAPRs-mediated antiviral innate immunity will be a very promising and valuable research field in the future
.
Link to the original text: https://pubmed.
ncbi.
nlm.
nih.
gov/33483164/ Brief introduction of the journal: Trends in Microbiology is a top journal in the field of microbiology under Cell Press.
It was founded in 1993 and mainly publishes an overview of new developments in the field of microbiology.
Including cell biology, immunology, genetics and microbial evolution, about 100 articles are published annually
.
Ranked 6th in the impact factor of all 134 specialized microbiological journals
.
The latest impact factor for 2020 is 17.
079
.
First author: Dr.
Zhu Huifang (Bachelor of Shenyang Pharmaceutical University, Master of Wuhan Institute of Virology, Chinese Academy of Sciences, Doctor of Kunming Institute of Botany, Chinese Academy of Sciences), First Affiliated Hospital of Gannan Medical College, Children's Medical Center, Department of Neonatology, Lecturer; concurrently served as Gannan Medical College, Basic medical school, master tutor
.
The main research directions include the exploration of the molecular mechanism of antiviral natural immunity and the immunotherapy of childhood leukemia tumors
.
Corresponding author: Professor Chunfu Zheng served as editor of mBio (zero breakthrough of Chinese local editors), editorial board member of Journal of Virology (one of the first two selected local editors in China); also served as Frontiers in Microbiology, Virology Journal, Journal of Medical Associate editor of Virology and guest editor of Frontiers in Immunology
.
Professor Zheng Chunfu has made breakthrough research results in the study of the molecular mechanism of the interaction between herpes simplex virus type I (HSV-1) infection and the host, and the study of HSV-1 escape host antiviral natural immunity.
He has made breakthroughs in Trends in Microbiology (IF 17.
079), Microbiology and Molecular Biology Reviews (cover article, IF 12.
568), FEMSMicrobiology Reviews (IF 16.
408), Blood (IF 22.
169), CellHost & Microbe (IF21.
023), Proceedings of the National Academy of Sciences USA (IF 11.
205), Protein and Cell ( IF 14.
870; 2 articles), mBio (IF 7.
867), Cytokine& Growth Factor Reviews (IF7.
658), Journal of Virology (23 articles, 2 of which are highlight articles; IF 5.
103), Journal of Immunology (2 articles, IF 5.
422) ) And other mainstream journals have published more than 100 SCI papers, with a total number of citations of more than 2,300, and an H-index of 28
.
It is worth mentioning that Professor Chunfu Zheng won the 2019-2020 Journal of Virology Annual Peer Review Ranking (TOP25 reviewers) and the 2019-2020 Global Publons Peer Review Award (TOP 1% in the field of microbiology)
.
Laboratory website: https://bms.
fjmu.
edu.
cn/2017/1130/c2905a72170/page.
htm The call for papers on the Frontiers in Microbiology subject by Professor Chunfu Zheng is still in progress, and the current deadline is October 31
.
15 articles have been published and 5 articles are under review
.
https:// is open for reprinting, welcome to forward to the circle of friends and WeChat group