Chasing Virus Replication and Infection: PAMP-PRR Interaction Drives Type I Interferon Production, Which in Turn Activates ISG Expression and ISGylation.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101509722 Publication Model: Electronic Cited Medium: Internet ISSN: 1999-4915 (Electronic) Linking ISSN: 19994915 NLM ISO Abbreviation: Viruses Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI

Interferon Type I*/immunology ; Interferon Type I*/metabolism ; Receptors, Pattern Recognition*/metabolism ; Receptors, Pattern Recognition*/immunology ; Cytokines*/metabolism ; Pathogen-Associated Molecular Pattern Molecules*/metabolism ; Pathogen-Associated Molecular Pattern Molecules*/immunology ; Virus Diseases*/immunology ; Virus Diseases*/virology ; Virus Replication* ; Host-Pathogen Interactions*; Ubiquitins/metabolism ; Humans ; Immunity, Innate ; Signal Transduction ; Animals

The innate immune response, particularly the interferon-mediated pathway, serves as the first line of defense against viral infections. During virus infection, viral pathogen-associated molecular patterns (PAMPs) are recognized by host pattern recognition receptors (PRRs), triggering downstream signaling pathways. This leads to the activation of transcription factors like IRF3, IRF7, and NF-κB, which translocate to the nucleus and induce the production of type I interferons (IFN-α and IFN-β). Once secreted, type I interferons bind to their receptors (IFNARs) on the surfaces of infected and neighboring cells, activating the JAK-STAT pathway. This results in the formation of the ISGF3 complex (composed of STAT1, STAT2, and IRF9), which translocates to the nucleus and drives the expression of interferon-stimulated genes (ISGs). Some ISGs exert antiviral effects by directly or indirectly blocking infection and replication. Among these ISGs, ISG15 plays a crucial role in the ISGylation process, a ubiquitin-like modification that tags viral and host proteins, regulating immune responses and inhibiting viral replication. However, viruses have evolved counteractive strategies to evade ISG15-mediated immunity and ISGylation. This review first outlines the PAMP-PRR-induced pathways leading to the production of cytokines and ISGs, followed by a summary of ISGylation's role in antiviral defense and viral evasion mechanisms targeting ISG15 and ISGYlation.

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U54 MD007597 United States MD NIMHD NIH HHS

Keywords: ISGylation; RNA viruses; antiviral; interferon (IFN); interferon-stimulated genes (ISGs); pathogen-associated molecular patterns (PAMPs); pattern recognition receptors (PRRs)

0 (Interferon Type I)
0 (Receptors, Pattern Recognition)
0 (Ubiquitins)
0 (Cytokines)
0 (Pathogen-Associated Molecular Pattern Molecules)
60267-61-0 (ISG15 protein, human)

Date Created: 20250426 Date Completed: 20250426 Latest Revision: 20250828

20260130

PMC12031425

10.3390/v17040528

40284971