TRIM25 and ZAP target the Ebola virus ribonucleoprotein complex to mediate interferon-induced restriction

Galão, Rui Pedro; Wilson, Harry; Bodmer, Bianca S.; Goldhill, Daniel H.; Hoenen, Thomas; Wilson, Sam J.; Swanson, Chad M.; Neil, Stuart J. D.

doi:10.1371/journal.ppat.1010530

Cited by 20 publications

(22 citation statements)

References 104 publications

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“…For example, the addition of TLR agonists (poly-ICLC, MPLA, CpG 2395, allydrogel) as adjuvants to filovirus virus-like particles augments protection against Ebola virus [164]. Furthermore, the E3 ubiquitin ligase TRIM25, which promotes RIG-I recognition of viral RNA, limits filovirus replication in an IFNdependent manner [165]. Targeting innate immune molecules involved in cytokine release and signaling has also shown preclinical promise, and inhibiting cytokine storm may be an effective strategy for many infectious and inflammatory diseases [162,166,167].…”

Section: Therapeutic Strategies and Preventionmentioning

confidence: 99%

Filoviruses: Innate Immunity, Inflammatory Cell Death, and Cytokines

Gullett

Kanneganti

2022

Pathogens

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Filoviruses are a group of single-stranded negative sense RNA viruses. The most well-known filoviruses that affect humans are ebolaviruses and marburgviruses. During infection, they can cause life-threatening symptoms such as inflammation, tissue damage, and hemorrhagic fever, with case fatality rates as high as 90%. The innate immune system is the first line of defense against pathogenic insults such as filoviruses. Pattern recognition receptors (PRRs), including toll-like receptors, retinoic acid-inducible gene-I-like receptors, C-type lectin receptors, AIM2-like receptors, and NOD-like receptors, detect pathogens and activate downstream signaling to induce the production of proinflammatory cytokines and interferons, alert the surrounding cells to the threat, and clear infected and damaged cells through innate immune cell death. However, filoviruses can modulate the host inflammatory response and innate immune cell death, causing an aberrant immune reaction. Here, we discuss how the innate immune system senses invading filoviruses and how these deadly pathogens interfere with the immune response. Furthermore, we highlight the experimental difficulties of studying filoviruses as well as the current state of filovirus-targeting therapeutics.

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Section: Therapeutic Strategies and Preventionmentioning

confidence: 99%

Filoviruses: Innate Immunity, Inflammatory Cell Death, and Cytokines

Gullett

Kanneganti

2022

Pathogens

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“…Butyrophilins were discovered originally as proteins involved in lactation and milk production, but they are now known to have immunomodulatory functions 3,[40][41][42] . These group of proteins have not been generally associated with antiviral properties, although one of two studies using ISG libraries against Ebola virus replicons identified BTN3A3 as a restriction factor for this virus 43,44 .…”

Section: Discussionmentioning

confidence: 99%

Zoonotic avian influenza viruses evade human BTN3A3 restriction

Pinto

Bakshi

Lytras

et al. 2022

Preprint

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Cross-species transmission of avian influenza A viruses (IAVs) into humans could represent the first step of a future pandemic1. Multiple factors limiting the spillover and adaptation of avian IAVs in humans have been identified, but they are not sufficient to explain which virus lineages are more likely to cross the species barrier1,2. Here, we identified human BTN3A33 (butyrophilin subfamily 3 member A3) as a potent inhibitor of avian but not human IAVs. We determined that BTN3A3 is constitutively expressed in human airways and its antiviral activity evolved in primates. We show that BTN3A3 restriction acts at the early stages of virus replication by inhibiting avian IAV vRNA transcription. We identified residue 313 in the viral nucleoprotein (NP) as the genetic determinant of BTN3A3 sensitivity (313F, or rarely 313L in avian viruses) or evasion (313Y or 313V in human viruses). However, several serotypes of avian IAVs that spilled over into humans in recent decades evade BTN3A3 restriction. In these cases, BTN3A3 evasion is due to substitutions (N, H or Q) in NP residue 52 that is adjacent to residue 313 in the NP structure4. Importantly, we identified more than 150 avian IAV lineages with a BTN3A3-resistant genotype. In conclusion, sensitivity or resistance to BTN3A3 is another factor to consider in the risk assessment of the zoonotic potential of avian influenza viruses.

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“…TRIM25 interacts with the viral helical ribonucleoprotein complex, causing its auto-ubiquitination and ubiquitination of the viral nucleoprotein. As can be seen, this process is independent of RIG-I, so in this case TRIM25 does not act on RLR receptors as a positive factor ( 115 ).…”

Section: Mechanism Of Action Of Rlr In Viral Hemorrhagic Fevermentioning

confidence: 99%

Factors affecting RIG-I-Like receptors activation - New research direction for viral hemorrhagic fevers

Małkowska

Niedźwiedzka-Rystwej

2022

Front. Immunol.

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Viral hemorrhagic fever (VHF) is a term referring to a group of life-threatening infections caused by several virus families (Arenaviridae, Bunyaviridae, Filoviridae and Flaviviridae). Depending on the virus, the infection can be mild and can be also characterized by an acute course with fever accompanied by hypervolemia and coagulopathy, resulting in bleeding and shock. It has been suggested that the course of the disease is strongly influenced by the activation of signaling pathways leading to RIG-I-like receptor-dependent interferon production. RIG-I-like receptors (RLRs) are one of two major receptor families that detect viral nucleic acid. RLR receptor activation is influenced by a number of factors that may have a key role in the differences that occur during the antiviral immune response in VHF. In the present study, we collected data on RLR receptors in viral hemorrhagic fevers and described factors that may influence the activation of the antiviral response. RLR receptors seem to be a good target for VHF research, which may contribute to better therapeutic and diagnostic strategies. However, due to the difficulty of conducting such studies in humans, we suggest using Lagovirus europaeus as an animal model for VHF.

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TRIM25 and ZAP target the Ebola virus ribonucleoprotein complex to mediate interferon-induced restriction

Cited by 20 publications

References 104 publications

Filoviruses: Innate Immunity, Inflammatory Cell Death, and Cytokines

Filoviruses: Innate Immunity, Inflammatory Cell Death, and Cytokines

Zoonotic avian influenza viruses evade human BTN3A3 restriction

Factors affecting RIG-I-Like receptors activation - New research direction for viral hemorrhagic fevers

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