Extracellular histones identified in crocodile blood inhibit in-vitro HIV-1 infection

Kozłowski, H; Lai, Eric T.L.; Havugimana, Pierre C.; White, Carl A.; Emili, Andrew; Sakac, Darinka; Binnington, Beth; Neschadim, Anton; McCarthy, Stephen D.S.; Branch, Donald R.

doi:10.1097/qad.0000000000001159

Cited by 24 publications

(22 citation statements)

References 31 publications

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“…Deiminated histone H3 is commonly used as an indicator for neutrophil extracellular trap formation (NETosis) [31,244], which has been related to PAD4 and implicated in anti-viral responses in cattle respiratory syncytial virus disease [42], in response to parasitic infections in cattle [245][246][247] as well as in response to certain antibiotics [248]. Interestingly, in crocodilians, extracellular histones H2A and H4 have been identified to act as inhibitors of viral (HIV) infection in vitro [249], although roles for post-translational deimination were not assessed. Anti-microbial effects for histones have furthermore been observed in teleost fish mucosal immunity for H2A [250] as well as for deiminated histone H3 [15].…”

Section: Discussionmentioning

confidence: 99%

Post-Translational Protein Deimination Signatures in Serum and Serum-Extracellular Vesicles of Bos taurus Reveal Immune, Anti-Pathogenic, Anti-Viral, Metabolic and Cancer-Related Pathways for Deimination

Criscitiello

Kraev

Lange

2020

IJMS

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The bovine immune system is known for its unusual traits relating to immunoglobulin and antiviral responses. Peptidylarginine deiminases (PADs) are phylogenetically conserved enzymes that cause post-translational deimination, contributing to protein moonlighting in health and disease. PADs also regulate extracellular vesicle (EV) release, forming a critical part of cellular communication. As PAD-mediated mechanisms in bovine immunology and physiology remain to be investigated, this study profiled deimination signatures in serum and serum-EVs in Bos taurus. Bos EVs were poly-dispersed in a 70-500 nm size range and showed differences in deiminated protein cargo, compared with whole sera. Key immune, metabolic and gene regulatory proteins were identified to be post-translationally deiminated with some overlapping hits in sera and EVs (e.g., immunoglobulins), while some were unique to either serum or serum-EVs (e.g., histones). Protein-protein interaction network analysis of deiminated proteins revealed KEGG pathways common for serum and serum-EVs, including complement and coagulation cascades, viral infection (enveloped viruses), viral myocarditis, bacterial and parasitic infections, autoimmune disease, immunodeficiency intestinal IgA production, B-cell receptor signalling, natural killer cell mediated cytotoxicity, platelet activation and hematopoiesis, alongside metabolic pathways including ferroptosis, vitamin digestion and absorption, cholesterol metabolism and mineral absorption. KEGG pathways specific to EVs related to HIF-1 signalling, oestrogen signalling and biosynthesis of amino acids. KEGG pathways specific for serum only, related to Epstein-Barr virus infection, transcription mis-regulation in cancer, bladder cancer, Rap1 signalling pathway, calcium signalling pathway and ECM-receptor interaction. This indicates differences in physiological and pathological pathways for deiminated proteins in serum-EVs, compared with serum. Our findings may shed light on pathways underlying a number of pathological and anti-pathogenic (viral, bacterial, parasitic) pathways, with putative translatable value to human pathologies, zoonotic diseases and development of therapies for infections, including anti-viral therapies.

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Section: Discussionmentioning

confidence: 99%

Post-Translational Protein Deimination Signatures in Serum and Serum-Extracellular Vesicles of Bos taurus Reveal Immune, Anti-Pathogenic, Anti-Viral, Metabolic and Cancer-Related Pathways for Deimination

Criscitiello

Kraev

Lange

2020

IJMS

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“…For example, the core histones H3 and H4 induce aggregation of seasonal influenza A particles and may inactivate HIV-1 ( 17 , 42 ). Intriguingly, extracellular histones also reduce HIV-1 transcription ( 43 ). Finally, histone H1 binds to noroviruses, the most common cause of viral gastroenteritis and prevents their attachment to intestinal cells ( 44 ).…”

Section: Antiviral Activity Of Netsmentioning

confidence: 99%

Neutrophil Extracellular Traps Go Viral

2016

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Neutrophils are the most numerous immune cells. Their importance as the first line of defense against bacterial and fungal pathogens is well described. In contrast, the role of neutrophils in controlling viral infections is less clear. Bacterial and fungal pathogens can stimulate neutrophils extracellular traps (NETs) in a process called NETosis. Although NETosis has previously been described as a special form of programmed cell death, there are forms of NET production that do not end with the demise of neutrophils. As an end result of NETosis, genomic DNA complexed with microbicidal proteins is expelled from neutrophils. These structures can kill pathogens or at least prevent their local spread within host tissue. On the other hand, disproportionate NET formation can cause local or systemic damage. Only recently, it was recognized that viruses can also induce NETosis. In this review, we discuss the mechanisms by which NETs are produced in the context of viral infection and how this may contribute to both antiviral immunity and immunopathology. Finally, we shed light on viral immune evasion mechanisms targeting NETs.

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“…dogs, rodents, horses) (Etulain et al , ; Li, Ng & Tablin, ; Vargas et al , ) and non‐mammal vertebrate species (e.g. crocodile, fish, chicken) (Palić et al , ; Kozlowski et al , ; Pieper et al , ; Wen et al , ), as well as for invertebrates such as the social amoeba Dictyostelium discoideum (Zhang et al , ) and the earthworm Eisenia andrei (Homa et al , ). Since most research on the topic of ETs has focused on neutrophils, we similarly focus on neutrophils and NET formation in this review.…”

Section: Introductionmentioning

confidence: 99%

Root extracellular traps versus neutrophil extracellular traps in host defence, a case of functional convergence?

et al. 2019

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The root cap releases cells that produce massive amounts of mucilage containing polysaccharides, proteoglycans, extracellular DNA (exDNA) and a variety of antimicrobial compounds. The released cells – known as border cells or border‐like cells – and mucilage secretions form networks that are defined as root extracellular traps (RETs). RETs are important players in root immunity. In animals, phagocytes are some of the most abundant white blood cells in circulation and are very important for immunity. These cells combat pathogens through multiple defence mechanisms, including the release of exDNA‐containing extracellular traps (ETs). Traps of neutrophil origin are abbreviated herein as NETs. Similar to phagocytes, plant root cap‐originating cells actively contribute to frontline defence against pathogens. RETs and NETs are thus components of the plant and animal immune systems, respectively, that exhibit similar compositional and functional properties. Herein, we describe and discuss the formation, molecular composition and functional similarities of these similar but different extracellular traps.

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Extracellular histones identified in crocodile blood inhibit in-vitro HIV-1 infection

Cited by 24 publications

References 31 publications

Post-Translational Protein Deimination Signatures in Serum and Serum-Extracellular Vesicles of Bos taurus Reveal Immune, Anti-Pathogenic, Anti-Viral, Metabolic and Cancer-Related Pathways for Deimination

Post-Translational Protein Deimination Signatures in Serum and Serum-Extracellular Vesicles of Bos taurus Reveal Immune, Anti-Pathogenic, Anti-Viral, Metabolic and Cancer-Related Pathways for Deimination

Neutrophil Extracellular Traps Go Viral

Root extracellular traps versus neutrophil extracellular traps in host defence, a case of functional convergence?

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