Interferon-Stimulated Genes in Antiviral Immunity

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Viral Immunology, Vaccines, and Antivirals".

Deadline for manuscript submissions: 31 May 2026 | Viewed by 530

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Guest Editor
Lady Davis Institute, Jewish General Hospital, McGill University, Montreal, QC H3T 1E2, Canada
Interests: pandemic and emerging viruses; host antiviral responses and HIV cure
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Special Issue Information

Dear Colleagues,

We are excited to launch this Special Issue on interferon-stimulated genes (ISGs) that protect hosts against viral infections through a rich variety of molecular mechanisms. In recent decades, significant progress has been made in elucidating the antiviral functions of individual ISGs and in deciphering the molecular details of their actions, ranging from early studies of OAS/RNase L and Mx proteins to systematic screening for ISGs that inhibit different classes of viruses. Despite these efforts, the functions of many ISGs remain unexplored, and there is limited research on how they act in concert to protect cells against viral infections and mitigate viral diseases in vivo. It is expected that much more work will be conducted on these fast-evolving fronts. 

This Special Issue invites the submission of manuscripts describing the antiviral functions of ISGs as well as viral counter-attack mechanisms. We particularly welcome studies on ISGs that encode non-coding RNA and on their roles during viral infections, as well as those on ISGs from species such as bats, birds, pigs, and other natural reservoirs of viruses that are sporadically transmitted to humans and cause pandemics. We encourage the submission of studies on how ISGs modulate cellular environments such as the metabolic state to deter viral replication. We also welcome studies aimed at revealing the operation of the ISG network with the application of systems biology and deep learning tools.

Prof. Dr. Chen Liang
Guest Editor

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Keywords

  • interferon-stimulated genes
  • ISGs
  • non-coding RNA
  • viral replication
  • deep learning tools

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Published Papers (1 paper)

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Research

19 pages, 2375 KB  
Article
The Intrinsic Innate Immunity of Hepatocytes Suppresses HBV Replication and Is Antagonized by HBx
by Chui Zeng, Fayed Attia Koutb Megahed, Yiqiong Guo, Dongmei Sun, Yaru Wang, Qin Liu, Yanwei Bi, Jinghang Li, Qi Zhou, Qingdong Xie, Pingnan Sun and Xiaoling Zhou
Viruses 2025, 17(12), 1599; https://doi.org/10.3390/v17121599 - 10 Dec 2025
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Abstract
(1) Background: Hepatitis B virus (HBV) belongs to the Hepadnaviridae family of viruses that interact with hepatocytes. HBV infection is a major global health problem. Most adults clear the infection quickly after being infected with HBV, while a few people develop chronic HBV [...] Read more.
(1) Background: Hepatitis B virus (HBV) belongs to the Hepadnaviridae family of viruses that interact with hepatocytes. HBV infection is a major global health problem. Most adults clear the infection quickly after being infected with HBV, while a few people develop chronic HBV infection. It is well-known that the early innate immune response of host cells plays an important role in the fight against virus infection. However, the interactions between HBV and the intrinsic innate immune system of hepatocytes are still not fully understood. The aim of this study was to confirm the interaction between HBV and hepatocytes, and to identify the interferon-stimulated genes (ISGs) regulated by HBx and their expression in association with HBV-associated HCC (HBV-HCC), so that we can refine our understanding of the interaction between HBV and ISGs and its potential influence on HBV-HCC. (2) Methods: We analyzed data concerning the stimulation of IFN-dependent genes in primary human hepatocytes (PHHs) transfected with pathogen DNA mimetics or infected with HBV in the GSE69590 database. Bioinformatic methods, such as GSEA, GO, and KEGG, were used to analyze the differentially expressed innate immunity genes and their related pathways to identify candidate intrinsic innate immune factors. qPCR on HepG2 and Huh7 cells, which highly express HBx, was used to detect relevant intrinsic innate immune factors. qPCR, RNAi, and Elisa methods were used to identify intrinsic innate immune factors in HBV-integrated HepG2.2.15 cells, and bioinformatics analysis was conducted on the HBV-infected tissues and cells in the GEO database. (3) Results: Inhibition of the JAK-STAT pathway enhanced HBV replication in HepG2 cells transfected with HBV plasmid and HepG2-NTCP cells infected with HBV. GSEA analysis of the GSE69590 data revealed significant changes in intrinsic innate immune pathways during HBV infection with PHH for 40 h. A total of 84 differentially expressed, candidate innate immunity genes were identified in GSE69590. Validation showed that TRIM22 and TRIM56 were down-regulated when HBx was expressed. Consistently, TRIM22 and TRIM56 were up-regulated following inhibition of HBx by transfection of HBx siRNA into HepG2.2.15 cells, and HBV pgRNA was up-regulated following down-regulated expression of TRIM22 and TRIM56 in HEK293 cells. Receiver operating characteristics (ROC) and overall survival (OS) analysis of 204 HBV-HCC patients showed that expression of TRIM22 was closely associated with HBV-HCC, and high expression of TRIM22 was associated with longer survival. (4) Conclusions: Innate immunity genes TRIM22 and TRIM56 are regulated by HBx, and higher expression of TRIM22 is closely related to longer survival of HBV-HCC patients. Full article
(This article belongs to the Special Issue Interferon-Stimulated Genes in Antiviral Immunity)
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