Explanipedia

Viral deISGylase activity antagonizes the host innate immune response and enhances coronavirus pathogenesis in a murine model of coronavirus infection 4265 Open

Mudassir Ali, Amornrat O’Brien, Fernando Moreira, Lucky Sarkar, Michaela U. Gack , et al. · 2025

Description Coronaviruses have evolved a breadth of mechanisms to antagonize host innate immune responses. One widely studied mechanism is the ability to deconjugate ISG15 from target proteins in a process called deISGylation, which is cat…

The RIG-I-like receptor family of immune proteins Open

Mariska van Huizen, Michaela U. Gack · 2025

Retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs) are crucial cytosolic RNA sensors in the innate immune defense against virus infections. RLRs recognize defined molecular features in viral RNAs; however, virus infection can als…

Dysregulation of innate immunity and cellular metabolism through virus-induced deISGylation Open

Junji Zhu, Guanqun Liu, Jielin Xu, Ke Li, Christopher M. Goins , et al. · 2025

SUMMARY Interferon-stimulated gene 15 (ISG15) regulates diverse cellular responses including antiviral immunity through its conjugation to proteins, a process known as ISGylation. Several pathogens, including SARS-CoV-2, subvert ISGylation…

Inhibition of coronaviral exonuclease activity by TRIM-mediated SUMOylation Open

Kannan Balakrishnan, Surajit Chakraborty, Cindy Chiang, Caleb M. Stratton, Anna A. Tumanova , et al. · 2025

Members of the TRIM E3 ligase family are effectors of the host innate or intrinsic defense against various viruses; however, how specific TRIM proteins antagonize coronavirus infection is still largely elusive. Through an RNAi screen targe…

Publisher Correction: TRIM23 mediates cGAS-induced autophagy in anti-HSV defense Open

Dhiraj Acharya, Zuberwasim Sayyad, Helene Hoenigsperger, Maximilian Hirschenberger, Matthew A. Zurenski , et al. · 2025

TRIM23 mediates cGAS-induced autophagy in anti-HSV defense Open

Dhiraj Acharya, Zuberwasim Sayyad, Helene Hoenigsperger, Maximilian Hirschenberger, Matthew A. Zurenski , et al. · 2025

Tearing down the house of mosquito-transmitted viruses Open

Shanti Pandey, Michaela U. Gack · 2025

MDA5 ISGylation is crucial for immune signaling to control viral replication and pathogenesis Open

Lucky Sarkar, Guanqun Liu, Dhiraj Acharya, Junji Zhu, Zuberwasim Sayyad , et al. · 2025

The posttranslational modification (PTM) of innate immune sensor proteins by ubiquitin or ubiquitin-like proteins is crucial for regulating antiviral host responses. The cytoplasmic dsRNA receptor melanoma differentiation-associated protei…

Nef stabilizes actin to prevent HIV-1 sensing by RIG-I-like receptors Open

Frank Kirchhoff, Alexandre Laliberté, Caterina Prelli Bozzo, Dhiraj Acharya, Aurora De Luna , et al. · 2025

Sensing of viral pathogens by RIG-I-like receptors (RLRs) requires their priming via dephosphorylation mediated by the protein phosphatase 1 regulatory subunit 12C (R12C), which is activated upon virus-induced actin rearrangements. Here, w…

TRIM Proteins: Key Regulators of Immunity to Herpesvirus Infection Open

Zuberwasim Sayyad, Dhiraj Acharya, Michaela U. Gack · 2024

Herpesviruses are ubiquitous DNA viruses that can establish latency and cause a range of mild to life-threatening diseases in humans. Upon infection, herpesviruses trigger the activation of several host antiviral defense programs that play…

MDA5 ISGylation is crucial for immune signaling to control viral replication and pathogenesis Open

Lucky Sarkar, Guanqun Liu, Dhiraj Acharya, Junji Zhu, Zuberwasim Sayyad , et al. · 2024

The posttranslational modification (PTM) of innate immune sensor proteins by ubiquitin or ubiquitin-like proteins is crucial for regulating antiviral host responses. The cytoplasmic dsRNA receptor melanoma differentiation-associated protei…

Inherited C-terminal TREX1 variants disrupt homology-directed repair to cause senescence and DNA damage phenotypes in Drosophila, mice, and humans Open

Samuel D. Chauvin, Shoichiro Ando, Joe A. Holley, Atsushi Sugie, Fang Zhao , et al. · 2024

ISGylation of the SARS-CoV-2 N protein by HERC5 impedes N oligomerization and thereby viral RNA synthesis Open

Junji Zhu, Guanqun Liu, Christopher M. Goins, Shaun R. Stauffer, Michaela U. Gack · 2024

Interferon (IFN)-stimulated gene 15 (ISG15), a ubiquitin-like protein, is covalently conjugated to host (immune) proteins such as MDA5 and IRF3 in a process called ISGylation, thereby limiting the replication of Severe acute respiratory sy…

ADAM9 promotes type I interferon-mediated innate immunity during encephalomyocarditis virus infection Open

Lindsey E. Bazzone, Junji Zhu, Michael R. King, Guanqun Liu, Zhiru Guo , et al. · 2024

Viral myocarditis, an inflammatory disease of the heart, causes significant morbidity and mortality. Type I interferon (IFN)-mediated antiviral responses protect against myocarditis, but the mechanisms are poorly understood. We previously …

HOIL1 mediates MDA5 activation through ubiquitination of LGP2 Open

Donghao Cheng, Junji Zhu, Guanqun Liu, Michaela U. Gack, Donna A. MacDuff · 2024

The RIG-I-like receptors (RLRs), RIG-I and MDA5, are innate sensors of RNA virus infections that are critical for mounting a robust antiviral immune response. We have shown previously that HOIL1, a component of the Linear Ubiquitin Chain A…

Hijacking of nucleotide biosynthesis and deamidation-mediated glycolysis by an oncogenic herpesvirus Open

Quanyuan Wan, Leah Tavakoli, Ting‐Yu Wang, Andrew J. Tucker, Ruiting Zhou , et al. · 2024

Atypical activation of the RNA sensor MDA5 by hepatitis C virus Open

Surajit Chakraborty, Junji Zhu, Michaela U. Gack · 2023

Hepatitis C virus (HCV) is a significant human pathogen that can cause a number of serious diseases including chronic inflammation of the liver, cirrhosis, and hepatocellular carcinoma. A key enzyme in the HCV life cycle is the nonstructur…

CSNK2 suppresses autophagy by activating FLN-NHL-containing TRIM proteins Open

Helene Hoenigsperger, Lennart Koepke, Dhiraj Acharya, Victoria Hunszinger, Dennis Freisem , et al. · 2023

Macroautophagy/autophagy is a tightly regulated cellular process integral to homeostasis and innate immunity. As such, dysregulation of autophagy is associated with cancer, neurodegenerative disorders, and infectious diseases. While numero…

ISG15: its roles in SARS-CoV-2 and other viral infections Open

Lucky Sarkar, Guanqun Liu, Michaela U. Gack · 2023

Cryo-EM structures of Uba7 reveal the molecular basis for ISG15 activation and E1-E2 thioester transfer Open

Mohammad Afsar, Guanqun Liu, Lijia Jia, Eliza A. Ruben, Digant Nayak , et al. · 2023

Acetylation of the NS3 helicase by KAT5γ is essential for flavivirus replication Open

Taryn M. Serman, Cindy Chiang, Guanqun Liu, Zuberwasim Sayyad, Shanti Pandey , et al. · 2023

Viral evasion of the interferon response at a glance Open

Junji Zhu, Cindy Chiang, Michaela U. Gack · 2023

Re-emerging and new viral pathogens have caused significant morbidity and mortality around the world, as evidenced by the recent monkeypox, Ebola and Zika virus outbreaks and the ongoing COVID-19 pandemic. Successful viral infection relies…

A viral pan-end RNA element and host complex define a SARS-CoV-2 regulon Open

Debjit Khan, Fulvia Terenzi, Guanqun Liu, Prabar K. Ghosh, Fengchun Ye , et al. · 2023

The RNA polymerase III–RIG-I axis in antiviral immunity and inflammation Open

Leslie Naesens, Filomeen Haerynck, Michaela U. Gack · 2023

An optimized circular polymerase extension reaction-based method for functional analysis of SARS-CoV-2 Open

Guanqun Liu, Michaela U. Gack · 2023

Background Reverse genetics systems have been crucial for studying specific viral genes and their relevance in the virus lifecycle, and become important tools for the rational attenuation of viruses and thereby for vaccine design. Recent r…

Supplementary Data from The BRCA1 Pseudogene Negatively Regulates Antitumor Responses through Inhibition of Innate Immune Defense Mechanisms Open

Yoo Jane Han, Jing Zhang, Jung Hyun Lee, Jennifer M. Mason, Olga Karginova , et al. · 2023

supplementary figures and table

Data from The BRCA1 Pseudogene Negatively Regulates Antitumor Responses through Inhibition of Innate Immune Defense Mechanisms Open

Yoo Jane Han, Jing Zhang, Jung Hyun Lee, Jennifer M. Mason, Olga Karginova , et al. · 2023

Innate immune defense mechanisms play a pivotal role in antitumor responses. Recent evidence suggests that antiviral innate immunity is regulated not only by exogenous non–self-RNA but also by host-derived pseudogene RNAs. A growing body o…

Supplementary Data from The BRCA1 Pseudogene Negatively Regulates Antitumor Responses through Inhibition of Innate Immune Defense Mechanisms Open

Yoo Jane Han, Jing Zhang, Jung Hyun Lee, Jennifer M. Mason, Olga Karginova , et al. · 2023

supplementary figures and table

Data from The BRCA1 Pseudogene Negatively Regulates Antitumor Responses through Inhibition of Innate Immune Defense Mechanisms Open

Yoo Jane Han, Jing Zhang, Jung Hyun Lee, Jennifer M. Mason, Olga Karginova , et al. · 2023

Innate immune defense mechanisms play a pivotal role in antitumor responses. Recent evidence suggests that antiviral innate immunity is regulated not only by exogenous non–self-RNA but also by host-derived pseudogene RNAs. A growing body o…

Virology under the Microscope—a Call for Rational Discourse Open

Felicia Goodrum, Anice C. Lowen, Seema S. Lakdawala, James C. Alwine, Arturo Casadevall , et al. · 2023

Viruses have brought humanity many challenges: respiratory infection, cancer, neurological impairment and immunosuppression to name a few. Virology research over the last 60+ years has responded to reduce this disease burden with vaccines …

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