Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Feb 24:13:839624.
doi: 10.3389/fmicb.2022.839624. eCollection 2022.

The Role of Deubiquitinases in Virus Replication and Host Innate Immune Response

Qinglin Zhang  1 , Qizhen Jia  1 , Wenying Gao  2 , Wenyan Zhang  2
Affiliations
Review

The Role of Deubiquitinases in Virus Replication and Host Innate Immune Response

Qinglin Zhang et al. Front Microbiol. .

Abstract

As a critical post-translational modification, ubiquitination is known to affect almost all the cellular processes including immunity, signaling pathways, cell death, cancer development, and viral infection by controlling protein stability. Deubiquitinases (DUBs) cleave ubiquitin from proteins and reverse the process of ubiquitination. Thus, DUBs play an important role in the deubiquitination process and serve as therapeutic targets for various diseases. DUBs are found in eukaryotes, bacteria, and viruses and influence various biological processes. Here, we summarize recent findings on the function of DUBs in modulating viral infection, the mechanism by which viral DUBs regulate host innate immune response, and highlight those DUBs that have recently been discovered as antiviral therapeutic targets.

Keywords: DUBs; PTM; antiviral innate immunity; ubiquitin; viral infection.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Regulation of host-encoded DUBs in innate immune response. Toll-like receptors (TLRs) are a type of pattern-recognition receptors (PRRs) that recognize pathogen-associated molecular patterns (PAMPs) and subsequently change their conformation to initiate downstream signaling. TLRs are located on the cell membrane, phagosome membrane, endosome, and endoplasmic reticulum (TLRs on endosomes and endoplasmic reticulum are not shown). TLRs can activate the expression of NF-κB or IRF3 and subsequently induce the expression of inflammatory cytokines or IFN-β in the nucleus. Activated TLRs recruit adaptor proteins, including TIRAP, MyD88, TRAM, and TRIF. First, the adaptors interact with IRAKs and TRAF6 and then activate NF-κB through the TAK1-IKK-IκB axis. Second, the adaptors mediate the expression of IRF3 via TRIF-TRAF3-TBK1 signaling. In addition, another PRR, RIG-I, which belongs to the RIG-I-like receptors (RLRs) family, is responsible for sensing RNA of pathogens. It interacts with MAVS, which further induces both NF-κB and IRF3. Stimulator of interferon genes (STING), located on the endoplasmic reticulum senses cytoplasmic DNA and regulates IFN signaling by activating TBK1 and IRF3. IFN-β induces the phosphorylation of JAK and expression of interferon-stimulated genes (ISGs) by activating the downstream JAK-STAT pathway. Host-encoded DUBs interact with the above signaling molecules to modulate the innate immune response. Their deubiquitinating function and substrates are shown in the schematic.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Akira S., Uematsu S., Takeuchi O. (2006). Pathogen recognition and innate immunity. Cell 124 783–801. 10.1016/j.cell.2006.02.015 - DOI - PubMed
    1. Ali A., Raja R., Farooqui S. R., Ahmad S., Banerjea A. C. (2017). USP7 deubiquitinase controls HIV-1 production by stabilizing Tat protein. Biochem. J. 474 1653–1668. 10.1042/BCJ20160304 - DOI - PubMed
    1. Atkins S. L., Motaib S., Wiser L. C., Hopcraft S. E., Hardy P. B., Shackelford J., et al. (2020). Small molecule screening identifies inhibitors of the Epstein-Barr virus deubiquitinating enzyme, BPLF1. Antiviral Res. 173:104649. 10.1016/j.antiviral.2019.104649 - DOI - PMC - PubMed
    1. Baker R. T., Tobias J. W., Varshavsky A. (1992). Ubiquitin-specific proteases of Saccharomyces cerevisiae. Cloning of UBP2 and UBP3, and functional analysis of the UBP gene family. J. Biol. Chem. 267 23364–23375. - PubMed
    1. Balakirev M. Y., Jaquinod M., Haas A. L., Chroboczek J. (2002). Deubiquitinating function of adenovirus proteinase. J. Virol. 76 6323–6331. 10.1128/jvi.76.12.6323-6331.2002 - DOI - PMC - PubMed