TRIM Proteins in Antiviral Immunity and Virus Pathogenesis

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

Deadline for manuscript submissions: 30 June 2024 | Viewed by 1925

Special Issue Editor


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Guest Editor
Center for Virus-Host-Innate Immunity and Department of Medicine; Rutgers Biomedical and Health Sciences, Institute for Infectious and Inflammatory Diseases, Rutgers University, Newark, NJ 07103, USA
Interests: innate immunity to virus infection and immune signaling; Type-I Interferons (IFN) and other inflammatory cytokines; the E3-ubiquitin ligase Tripartite Motif (TRIM) family of proteins in immunity and virus pathogenesis; the role of ubiquitin in immunity and virus replication; viral evasion mechanisms; the role of the ubiquitin system in replication of viruses including Ebola, Nipah, dengue, Zika, Influenza, and SARS-CoV-2; virus‒host interactions and viral pathogenesis via the ubiquitin system; emerging proviral roles of TRIM proteins
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Special Issue Information

Dear Colleagues,

Tripartite Motif (TRIM) proteins belong to a large family of E3-ubiquitin ligases, many of which have antiviral activity. TRIMs have long been known for their functions as direct restriction factors; however, they can also act indirectly by promoting the induction of antiviral type-I Interferons (IFN-I). TRIM activity has been linked to a variety of cellular functions, including the regulation of immune signaling, cell cycle, apoptosis, autophagy, and many others. Studies are uncovering unrecognized mechanisms of TRIM activity, including the direct ubiquitination of viral proteins that may balance proviral and antiviral functions, and may perform this via the synthesis of unconventional polyubiquitin chains. It is still unclear what mechanism balances the contradictory roles of TRIMs at the physiological level. The dual roles of TRIMs and their involvement in multiple cellular functions have made it virtually impossible to use them as feasible druggable targets. The generation of TRIM knockouts in cells and animals using CRISPR technology has led to an exponential advance in our understanding of TRIM functions. In this Special Issue, we will explore novel aspects of TRIM function in relation to virus infection, including proviral and antiviral roles, antagonism, and pathogenesis. New comprehensive studies may help identify novel strategies to modulate TRIM activity for therapeutic interventions.

Dr. Ricardo Rajsbaum
Guest Editor

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Keywords

  • Tripartite Motif (TRIM) proteins
  • E3-Ubiquitin ligases
  • innate immunity
  • antiviral restriction factors
  • proviral functions
  • Type-I Interferons (IFN-I)
  • inflammatory cytokines
  • ubiquitin
  • ubiquitin-like proteins
  • viral antagonism
  • autophagy
  • viral pathogenesis

Published Papers (1 paper)

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Research

17 pages, 2446 KiB  
Article
Pteropus vampyrus TRIM40 Is an Interferon-Stimulated Gene That Antagonizes RIG-I-like Receptors
by Sarah van Tol, Adam Hage, Ricardo Rajsbaum and Alexander N. Freiberg
Viruses 2023, 15(11), 2147; https://doi.org/10.3390/v15112147 - 25 Oct 2023
Viewed by 1187
Abstract
Nipah virus (NiV; genus: Henipavirus; family: Paramyxoviridae) naturally infects Old World fruit bats (family Pteropodidae) without causing overt disease. Conversely, NiV infection in humans and other mammals can be lethal. Comparing bat antiviral responses with those of humans may illuminate the [...] Read more.
Nipah virus (NiV; genus: Henipavirus; family: Paramyxoviridae) naturally infects Old World fruit bats (family Pteropodidae) without causing overt disease. Conversely, NiV infection in humans and other mammals can be lethal. Comparing bat antiviral responses with those of humans may illuminate the mechanisms that facilitate bats’ tolerance. Tripartite motif proteins (TRIMs), a large family of E3-ubiquitin ligases, fine-tune innate antiviral immune responses, and two human TRIMs interact with Henipavirus proteins. We hypothesize that NiV infection induces the expression of an immunosuppressive TRIM in bat, but not human cells, to promote tolerance. Here, we show that TRIM40 is an interferon-stimulated gene (ISG) in pteropodid but not human cells. Knockdown of bat TRIM40 increases gene expression of IFNβ, ISGs, and pro-inflammatory cytokines following poly(I:C) transfection. In Pteropus vampyrus, but not human cells, NiV induces TRIM40 expression within 16 h after infection, and knockdown of TRIM40 correlates with reduced NiV titers as compared to control cells. Bats may have evolved to express TRIM40 in response to viral infections to control immunopathogenesis. Full article
(This article belongs to the Special Issue TRIM Proteins in Antiviral Immunity and Virus Pathogenesis)
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