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Viruses
Special Issues
STING-Mediated Antiviral Activity and Viral Evasion
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STING-Mediated Antiviral Activity and Viral Evasion

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

Deadline for manuscript submissions: closed (31 March 2024) | Viewed by 7028

Special Issue Editors

Dr. Yanmin Li

E-Mail Website
Guest Editor
College of Animal Husbandry and Veterinary Medicine, Southwest University for Nationalities, Chengdu 610041, China
Interests: viral infection; innate immunity; diagnostic assay; animals; pathogenesis of viral diseases; vaccine
Special Issues, Collections and Topics in MDPI journals
Dr. Zhidong Zhang

E-Mail Website
Guest Editor
College of Animal Husbandry and Veterinary Medicine, Southwest University for Nationalities, Chengdu 610041, China
Interests: pathogenesis of viral diseases; interaction of a virus with host; diagnostic assay
Special Issues, Collections and Topics in MDPI journals
Dr. Xiaodong Qin

E-Mail Website
Guest Editor
Chinese Academy of Agricultural Sciences, Beijing 100081, China
Interests: viral infection; innate immunity; diagnostic assay; animals; pathogenesis of viral diseases; vaccine

Special Issue Information

Dear Colleagues,

A stimulator of interferon genes (STING) is a transmembrane protein on the endoplasmic reticulum. It is not only an essential regulator of innate immunity in relation to infection with DNA viruses by sensing viral DNA via the cGAS-STING pathway, but also plays a fundamental role in responses against RNA viruses by regulating autophagy, cellular translation machinery, and the crosstalk with RNA RLRs (RIG-I and MDA5). However, numerous factors, particularly viral factors that dysregulate STING and its dependent pathway network, have been shown to help viruses to escape innate immune response to benefit the survival of viruses. Therefore, STING is a signaling hub in innate immunity against viral infection and the activation of STING pathway may provide a new therapeutic approach to fighting against infections with viruses. A better understanding of the regulating mechanisms and signaling pathways of STING associated with innate immunity to viral infection can shed light on new targets for novel antiviral therapeutics and vaccines. This Special Issue is intended to highlight novel findings related to STING and its pathway network in regulating viral replication, antiviral immunity, and cell death, as well as the development of novel broadly antiviral drugs and vaccines.

Dr. Yanmin Li
Dr. Zhidong Zhang
Dr. Xiaodong Qin
Guest Editors

Manuscript Submission Information

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • STING
  • viral infection
  • innate immunity
  • antiviral
  • viral evasion

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Published Papers (4 papers)

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Research

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16 pages, 1241 KiB  
Article
STING Orchestrates EV-D68 Replication and Immunometabolism within Viral-Induced Replication Organelles
by Kathy Triantafilou, Barbara Szomolay, Mark William Shepherd, Joshi Ramanjulu and Martha Triantafilou
Viruses 2024, 16(10), 1541; https://doi.org/10.3390/v16101541 - 29 Sep 2024
Viewed by 728
Abstract
Some respiratory viruses, such as Human Rhinovirus, SARS-CoV-2, and Enterovirus D-68 (EV-D68), share the feature of hijacking host lipids in order to generate specialised replication organelles (ROs) with unique lipid compositions to enable viral replication. We have recently uncovered a novel non-canonical function [...] Read more.
Some respiratory viruses, such as Human Rhinovirus, SARS-CoV-2, and Enterovirus D-68 (EV-D68), share the feature of hijacking host lipids in order to generate specialised replication organelles (ROs) with unique lipid compositions to enable viral replication. We have recently uncovered a novel non-canonical function of the stimulator of interferon genes (STING) pathway, as a critical factor in the formation of ROs in response to HRV infection. The STING pathway is the main DNA virus sensing system of the innate immune system controlling the type I IFN machinery. Although it is well-characterised as part of the DNA sensor machinery, the STING function in RNA viral infections is largely unexplored. In the current study, we investigated whether other RO-forming RNA viruses, such as EV-D68 and SARS-CoV-2, can also utilise STING for their replication. Using genetic and pharmacological inhibition, we demonstrate that STING is hijacked by these viruses and is utilised as part of the viral replication machinery. STING also co-localises with glycolytic enzymes needed to fuel the energy for replication. The inhibition of STING leads to the modulation of glucose metabolism in EV-D68-infected cells, suggesting that it might also manipulate immunometabolism. Therefore, for RO-generating RNA viruses, STING seems to have non-canonical functions in membrane lipid re-modelling, and the formation of replication vesicles, as well as immunometabolism. Full article
(This article belongs to the Special Issue STING-Mediated Antiviral Activity and Viral Evasion)
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12 pages, 2573 KiB  
Article
Stimulator of Interferon Gene Agonists Induce an Innate Antiviral Response against Influenza Viruses
by Hyun Jung Lee, Joo-Hoo Park, Il-Ho Park and Ok Sarah Shin
Viruses 2024, 16(6), 855; https://doi.org/10.3390/v16060855 - 27 May 2024
Viewed by 1508
Abstract
The devastating effects of COVID-19 have highlighted the importance of prophylactic and therapeutic strategies to combat respiratory diseases. Stimulator of interferon gene (STING) is an essential component of the host defense mechanisms against respiratory viral infections. Although the role of the cGAS/STING signaling [...] Read more.
The devastating effects of COVID-19 have highlighted the importance of prophylactic and therapeutic strategies to combat respiratory diseases. Stimulator of interferon gene (STING) is an essential component of the host defense mechanisms against respiratory viral infections. Although the role of the cGAS/STING signaling axis in the innate immune response to DNA viruses has been thoroughly characterized, mounting evidence shows that it also plays a key role in the prevention of RNA virus infections. In this study, we investigated the role of STING activation during Influenza virus (IFV) infection. In both mouse bone marrow-derived macrophages and monocytic cell line THP-1 differentiated with PMA, we found that dimeric amidobenzimidazole (diABZI), a STING agonist, had substantial anti-IFV activity against multiple strains of IFV, including A/H1N1, A/H3N2, B/Yamagata, and B/Victoria. On the other hand, a pharmacological antagonist of STING (H-151) or the loss of STING in human macrophages leads to enhanced viral replication but suppressed IFN expression. Furthermore, diABZI was antiviral against IFV in primary air–liquid interface cultures of nasal epithelial cells. Our data suggest that STING agonists may serve as promising therapeutic antiviral agents to combat IFV. Full article
(This article belongs to the Special Issue STING-Mediated Antiviral Activity and Viral Evasion)
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13 pages, 2985 KiB  
Article
A Non-Nucleotide STING Agonist MSA-2 Synergized with Manganese in Enhancing STING Activation to Elicit Potent Anti-RNA Virus Activity in the Cells
by Hanrui Lin, Rui Zhang, Hanyi Xiang, Xinqian Lin, Xiongting Huang, Jingsong Chen, Long Zhou, Zhidong Zhang and Yanmin Li
Viruses 2023, 15(11), 2138; https://doi.org/10.3390/v15112138 - 24 Oct 2023
Cited by 3 | Viewed by 1774
Abstract
Both Manganese (Mn2+) and MSA-2 can activate the downstream signal pathway through stimulator of interferon genes (STING) and induce the expression of type I interferon, which is important for hosts to protect against DNA viruses. However, its effect on RNA viruses [...] Read more.
Both Manganese (Mn2+) and MSA-2 can activate the downstream signal pathway through stimulator of interferon genes (STING) and induce the expression of type I interferon, which is important for hosts to protect against DNA viruses. However, its effect on RNA viruses remains unknown. In this study, we used Seneca Valley virus (SVV) as a model RNA virus to investigate the inhibitory effects of Mn2+ and MSA-2 on the virus replication in the porcine cells (PK-15 cells). The results showed that both MSA-2 and Mn2+ were able to inhibit the SVV replication in PK-15 cells. The combination of MAS-2 and Mn2+ could confer better protection against SVV. Further studies showed that MSA-2 and Mn2+ could activate TBK1, IRF3 and NFκB through STING and induce the expression of IFN-β, IL-6 and TNF-α. The present study confirmed that MSA-2 synergized with Mn2+ in STING activation to generate a better antiviral effect in vitro, which would be helpful for the further development of effective antiviral drugs in the future. Full article
(This article belongs to the Special Issue STING-Mediated Antiviral Activity and Viral Evasion)
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Review

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32 pages, 1119 KiB  
Review
STINGing Defenses: Unmasking the Mechanisms of DNA Oncovirus-Mediated Immune Escape
by Mayra F Martínez-López, Claire Muslin and Nikolaos C. Kyriakidis
Viruses 2024, 16(4), 574; https://doi.org/10.3390/v16040574 - 9 Apr 2024
Viewed by 2297
Abstract
DNA oncoviruses represent an intriguing subject due to their involvement in oncogenesis. These viruses have evolved mechanisms to manipulate the host immune response, facilitating their persistence and actively contributing to carcinogenic processes. This paper describes the complex interactions between DNA oncoviruses and the [...] Read more.
DNA oncoviruses represent an intriguing subject due to their involvement in oncogenesis. These viruses have evolved mechanisms to manipulate the host immune response, facilitating their persistence and actively contributing to carcinogenic processes. This paper describes the complex interactions between DNA oncoviruses and the innate immune system, with a particular emphasis on the cGAS-STING pathway. Exploring these interactions highlights that DNA oncoviruses strategically target and subvert this pathway, exploiting its vulnerabilities for their own survival and proliferation within the host. Understanding these interactions lays the foundation for identifying potential therapeutic interventions. Herein, we sought to contribute to the ongoing efforts in advancing our understanding of the innate immune system in oncoviral pathogenesis. Full article
(This article belongs to the Special Issue STING-Mediated Antiviral Activity and Viral Evasion)
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