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Article: Exosome-Mediated Antigen Delivery: Unveiling Novel Strategies in Viral Infection Control and Vaccine Design.

El Safadi, Daed / Mokhtari, Alexandre / Krejbich, Morgane / Lagrave, Alisé / Hirigoyen, Ugo / Lebeau, Grégorie / Viranaicken, Wildriss / Krejbich-Trotot, Pascale

Vaccines

2024 Volume 12, Issue 3

Abstract: Exosomes are small subtypes of extracellular vesicles (EVs) naturally released by different types of cells into their environment. Their physiological roles appear to be multiple, yet many aspects of their biological activities remain to be understood. ... ...

Abstract	Exosomes are small subtypes of extracellular vesicles (EVs) naturally released by different types of cells into their environment. Their physiological roles appear to be multiple, yet many aspects of their biological activities remain to be understood. These vesicles can transport and deliver a variety of cargoes and may serve as unconventional secretory vesicles. Thus, they play a crucial role as important vectors for intercellular communication and the maintenance of homeostasis. Exosome production and content can vary under several stresses or modifications in the cell microenvironment, influencing cellular responses and stimulating immunity. During infectious processes, exosomes are described as double-edged swords, displaying both beneficial and detrimental effects. Owing to their tractability, the analysis of EVs from multiple biofluids has become a booming tool for monitoring various pathologies, from infectious to cancerous origins. In this review, we present an overview of exosome features and discuss their particular and ambiguous functions in infectious contexts. We then focus on their properties as diagnostic or therapeutic tools. In this regard, we explore the capacity of exosomes to vectorize immunogenic viral antigens and their function in mounting adaptive immune responses. As exosomes provide interesting platforms for antigen presentation, we further review the available data on exosome engineering, which enables peptides of interest to be exposed at their surface. In the light of all these data, exosomes are emerging as promising avenues for vaccine strategies.
Language	English
Publishing date	2024-03-07
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2703319-3
ISSN	2076-393X
ISSN	2076-393X
DOI	10.3390/vaccines12030280
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Article ; Online: Zika virus restriction of host antioxidant response is mediated by intracellular NS1 and reveals its ability to upregulate Bach1 expression.

Lebeau, Grégorie / El Safadi, Daed / Hoarau, Mathilde / Meilhac, Olivier / Krejbich-Trotot, Pascale / Viranaicken, Wildriss

Biochemical and biophysical research communications

2023 Volume 690, Page(s) 149312

Abstract: Zika virus (ZIKV), has gained global attention due to its association with severe disorders, including microcephaly and congenital Zika syndrome. We investigated the role of ZIKV nonstructural protein 1 (NS1) in altering the host's antioxidant response. ... ...

Abstract	Zika virus (ZIKV), has gained global attention due to its association with severe disorders, including microcephaly and congenital Zika syndrome. We investigated the role of ZIKV nonstructural protein 1 (NS1) in altering the host's antioxidant response. Using a stable cell line expressing NS1, we found that NS1 significantly reduced the expression of antioxidant-related genes, including heme oxygenase 1 (HO-1), NAD(P)H quinone dehydrogenase 1 (NQO1), and sequestosome-1 (SQSTM1), which are regulated NRF2. Interestingly, this effect was attributed to increased expression of BACH1, a factor that competes with NRF2 for binding to certain antioxidant responsive elements (ARE). Thus, ZIKV NS1-mediated disruption of the antioxidant system is linked to BACH1 overexpression. These findings offer insights into ZIKV pathogenesis and suggest potential therapeutic strategies targeting the NRF2-BACH1 axis.
MeSH term(s)	Humans ; Zika Virus/metabolism ; Antioxidants ; NF-E2-Related Factor 2/metabolism ; Zika Virus Infection ; Cell Line ; Viral Nonstructural Proteins/genetics
Chemical Substances	Antioxidants ; NF-E2-Related Factor 2 ; Viral Nonstructural Proteins
Language	English
Publishing date	2023-11-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	205723-2
ISSN	1090-2104 ; 0006-291X ; 0006-291X
ISSN (online)	1090-2104 ; 0006-291X
ISSN	0006-291X
DOI	10.1016/j.bbrc.2023.149312
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Article ; Online: Cell cycle and mitosis progression during ZIKA virus infection: The viral non-structural protein NS5 as a master regulator of the APC/cyclosome?

Lebeau, Grégorie / Hoareau, Mathilde / Rivière, Sébastien / El Safadi, Daed / Da Silva, Christine Robert / Krejbich-Trotot, Pascale / Viranaicken, Wildriss

Biochimie

2024 Volume 221, Page(s) 75–80

Abstract: Alterations in cell cycle regulation contribute to Zika virus (ZIKV)-associated pathogenesis and may have implications for the development of therapeutic avenues. As a matter of fact, ZIKV alters cell cycle progression at multiple stages, including G1, S, ...

Abstract	Alterations in cell cycle regulation contribute to Zika virus (ZIKV)-associated pathogenesis and may have implications for the development of therapeutic avenues. As a matter of fact, ZIKV alters cell cycle progression at multiple stages, including G1, S, G2, and M phases. During a cell cycle, the progression of mitosis is particularly controlled to avoid any abnormalities in cell division. In this regard, the critical metaphase-anaphase transition is triggered by the activation of anaphase-promoting complex/cyclosome (APC/C) by its E3 ubiquitin ligase subunit Cdc20. Cdc20 recognizes substrates by interacting with a destruction box motif (D-box). Recently, the ZIKV nonstructural protein 5 (NS5), one of the most highly conserved flavivirus proteins, has been shown to localize to the centrosome in each pole and to spindle fibers during mitosis. Inducible expression of NS5 reveals an interaction of this viral factor with centrosomal proteins leading to an increase in the time required to complete mitosis. By analyzing the NS5 sequence, we discovered the presence of a D-box. Taken together, these data support the idea that, in addition to its role in viral replication, NS5 plays a critical role in the control of the cell cycle of infected cells and, more specifically, in the regulation of the mitotic spindle. Here we propose that the NS5 protein may interfere with the metaphase-anaphase progression, and thus cause the observed delay in mitosis via the regulation of APC/C.
Language	English
Publishing date	2024-02-01
Publishing country	France
Document type	Journal Article
ZDB-ID	120345-9
ISSN	1638-6183 ; 0300-9084
ISSN (online)	1638-6183
ISSN	0300-9084
DOI	10.1016/j.biochi.2024.01.016
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Article ; Online: The Antiviral Potential of AdipoRon, an Adiponectin Receptor Agonist, Reveals the Ability of Zika Virus to Deregulate Adiponectin Receptor Expression.

El Safadi, Daed / Lebeau, Grégorie / Turpin, Jonathan / Lefebvre d'Hellencourt, Christian / Diotel, Nicolas / Viranaicken, Wildriss / Krejbich-Trotot, Pascale

Viruses

2023 Volume 16, Issue 1

Abstract: Zika virus (ZIKV) is a pathogenic member of the flavivirus family, with several unique characteristics. Unlike any other arbovirus, ZIKV can be transmitted sexually and maternally, and thus produce congenital syndromes (CZS) due to its neurotropism. This ...

Abstract	Zika virus (ZIKV) is a pathogenic member of the flavivirus family, with several unique characteristics. Unlike any other arbovirus, ZIKV can be transmitted sexually and maternally, and thus produce congenital syndromes (CZS) due to its neurotropism. This challenges the search for safe active molecules that can protect pregnant women and their fetuses. In this context, and in the absence of any existing treatment, it seemed worthwhile to test whether the known cytoprotective properties of adiponectin and its pharmacological analog, AdipoRon, could influence the outcome of ZIKV infection. We showed that both AdipoRon and adiponectin could significantly reduce the in vitro infection of A549 epithelial cells, a well-known cell model for flavivirus infection studies. This effect was particularly observed when a pre-treatment was carried out. Conversely, ZIKV revealed an ability to downregulate adiponectin receptor expression and thereby limit adiponectin signaling.
MeSH term(s)	Pregnancy ; Female ; Humans ; Zika Virus ; Zika Virus Infection/drug therapy ; Adiponectin ; Receptors, Adiponectin ; Antiviral Agents/pharmacology ; Piperidines
Chemical Substances	AdipoRon ; Adiponectin ; Receptors, Adiponectin ; Antiviral Agents ; Piperidines
Language	English
Publishing date	2023-12-22
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v16010024
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Article ; Online: The Influence of Metabolism on Immune Response: A Journey to Understand Immunometabolism in the Context of Viral Infection.

El Safadi, Daed / Paulo-Ramos, Aurélie / Hoareau, Mathilde / Roche, Marjolaine / Krejbich-Trotot, Pascale / Viranaicken, Wildriss / Lebeau, Grégorie

Viruses

2023 Volume 15, Issue 12

Abstract: In recent years, the emergence of the concept of immunometabolism has shed light on the pivotal role that cellular metabolism plays in both the activation of immune cells and the development of immune programs. The antiviral response, a widely ... ...

Abstract	In recent years, the emergence of the concept of immunometabolism has shed light on the pivotal role that cellular metabolism plays in both the activation of immune cells and the development of immune programs. The antiviral response, a widely distributed defense mechanism used by infected cells, serves to not only control infections but also to attenuate their deleterious effects. The exploration of the role of metabolism in orchestrating the antiviral response represents a burgeoning area of research, especially considering the escalating incidence of viral outbreaks coupled with the increasing prevalence of metabolic diseases. Here, we present a review of current knowledge regarding immunometabolism and the antiviral response during viral infections. Initially, we delve into the concept of immunometabolism by examining its application in the field of cancer-a domain that has long spearheaded inquiries into this fascinating intersection of disciplines. Subsequently, we explore examples of immune cells whose activation is intricately regulated by metabolic processes. Progressing with a systematic and cellular approach, our aim is to unravel the potential role of metabolism in antiviral defense, placing significant emphasis on the innate and canonical interferon response.
MeSH term(s)	Humans ; Virus Diseases ; Interferons ; Metabolic Diseases ; Antiviral Agents
Chemical Substances	Interferons (9008-11-1) ; Antiviral Agents
Language	English
Publishing date	2023-12-09
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v15122399
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Article: Evidence of RedOX Imbalance during Zika Virus Infection Promoting the Formation of Disulfide-Bond-Dependent Oligomers of the Envelope Protein

Lebeau, Grégorie / Turpin, Jonathan / Frumence, Etienne / El Safadi, Daed / Harrabi, Wissal / Desprès, Philippe / Krejbich-Trotot, Pascale / Viranaïcken, Wildriss

Viruses. 2022 May 24, v. 14, no. 6

2022

Abstract: Flaviviruses replicate in membrane factories associated with the endoplasmic reticulum (ER). Significant levels of flavivirus viral protein accumulation contribute to ER stress. As a consequence, the host cell exhibits an Unfolded Protein Response (UPR), ...

Abstract	Flaviviruses replicate in membrane factories associated with the endoplasmic reticulum (ER). Significant levels of flavivirus viral protein accumulation contribute to ER stress. As a consequence, the host cell exhibits an Unfolded Protein Response (UPR), subsequently stimulating appropriate cellular responses such as adaptation, autophagy or apoptosis. The correct redox conditions of this compartment are essential to forming native disulfide bonds in proteins. Zika virus (ZIKV) has the ability to induce persistent ER stress leading to the activation of UPR pathways. In this study, we wondered whether ZIKV affects the redox balance and consequently the oxidative protein folding in the ER. We found that ZIKV replication influences the redox state, leading to the aggregation of the viral envelope protein as amyloid-like structures in the infected cells.
Keywords	Zika virus ; apoptosis ; autophagy ; disulfides ; endoplasmic reticulum ; unfolded protein response ; viral envelope proteins
Language	English
Dates of publication	2022-0524
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2516098-9
ISSN	1999-4915
ISSN	1999-4915
DOI	10.3390/v14061131
Database	NAL-Catalogue (AGRICOLA)

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Article: Improvement of immunodetection of the transcription factor C/EBP homologous protein by western blot

Turpin, Jonathan / Frumence, Etienne / El Safadi, Daed / Meilhac, Olivier / Krejbich-Trotot, Pascale / Viranaïcken, Wildriss

Analytical biochemistry. 2020 July 15, v. 601

2020

Abstract: Accumulation of misfolded proteins within the endoplasmic reticulum (ER) induces an unfolded protein response (UPR) that either restores homeostasis or triggers apoptosis in case of adaptation failure. The three activated branches of UPR lead to IRE1-, ... ...

Abstract	Accumulation of misfolded proteins within the endoplasmic reticulum (ER) induces an unfolded protein response (UPR) that either restores homeostasis or triggers apoptosis in case of adaptation failure. The three activated branches of UPR lead to IRE1-, PERK- and ATF6- dependent transcriptional induction of the gene encoding the transcription factor C/EBP homologous protein (CHOP) which plays an important role in apoptosis induction. In conventional immunoblotting conditions, detection of CHOP is a difficult task. Using a fixation step, we have optimized the detection of CHOP and this method provides a valuable tool to decipher CHOP involvement in UPR.
Keywords	Western blotting ; apoptosis ; branches ; detection ; endoplasmic reticulum ; genes ; homeostasis ; lead ; transcription (genetics) ; transcription factors ; unfolded protein response
Language	English
Dates of publication	2020-0715
Publishing place	Elsevier Inc.
Document type	Article
Note	NAL-light
ZDB-ID	1110-1
ISSN	1096-0309 ; 0003-2697
ISSN (online)	1096-0309
ISSN	0003-2697
DOI	10.1016/j.ab.2020.113775
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Evidence of RedOX Imbalance during Zika Virus Infection Promoting the Formation of Disulfide-Bond-Dependent Oligomers of the Envelope Protein.

Lebeau, Grégorie / Turpin, Jonathan / Frumence, Etienne / El Safadi, Daed / Harrabi, Wissal / Desprès, Philippe / Krejbich-Trotot, Pascale / Viranaïcken, Wildriss

Viruses

2022 Volume 14, Issue 6

Abstract	Flaviviruses replicate in membrane factories associated with the endoplasmic reticulum (ER). Significant levels of flavivirus viral protein accumulation contribute to ER stress. As a consequence, the host cell exhibits an Unfolded Protein Response (UPR), subsequently stimulating appropriate cellular responses such as adaptation, autophagy or apoptosis. The correct redox conditions of this compartment are essential to forming native disulfide bonds in proteins. Zika virus (ZIKV) has the ability to induce persistent ER stress leading to the activation of UPR pathways. In this study, we wondered whether ZIKV affects the redox balance and consequently the oxidative protein folding in the ER. We found that ZIKV replication influences the redox state, leading to the aggregation of the viral envelope protein as amyloid-like structures in the infected cells.
MeSH term(s)	Disulfides ; Endoplasmic Reticulum Stress ; Flavivirus/metabolism ; Humans ; Oxidation-Reduction ; Unfolded Protein Response ; Virus Replication/physiology ; Zika Virus/physiology ; Zika Virus Infection
Chemical Substances	Disulfides
Language	English
Publishing date	2022-05-24
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v14061131
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Article ; Online: Apoptosis during ZIKA Virus Infection: Too Soon or Too Late?

Turpin, Jonathan / El Safadi, Daed / Lebeau, Grégorie / Krejbich, Morgane / Chatelain, Camille / Desprès, Philippe / Viranaïcken, Wildriss / Krejbich-Trotot, Pascale

International journal of molecular sciences

2022 Volume 23, Issue 3

Abstract: Cell death by apoptosis is a major cellular response in the control of tissue homeostasis and as a defense mechanism in the case of cellular aggression such as an infection. Cell self-destruction is part of antiviral responses, aimed at limiting the ... ...

Abstract	Cell death by apoptosis is a major cellular response in the control of tissue homeostasis and as a defense mechanism in the case of cellular aggression such as an infection. Cell self-destruction is part of antiviral responses, aimed at limiting the spread of a virus. Although it may contribute to the deleterious effects in infectious pathology, apoptosis remains a key mechanism for viral clearance and the resolution of infection. The control mechanisms of cell death processes by viruses have been extensively studied. Apoptosis can be triggered by different viral determinants through different pathways as a result of virally induced cell stresses and innate immune responses. Zika virus (ZIKV) induces Zika disease in humans, which has caused severe neurological forms, birth defects, and microcephaly in newborns during the last epidemics. ZIKV also surprised by revealing an ability to persist in the genital tract and in semen, thus being sexually transmitted. Mechanisms of diverting antiviral responses such as the interferon response, the role of cytopathic effects and apoptosis in the etiology of the disease have been widely studied and debated. In this review, we examined the interplay between ZIKV infection of different cell types and apoptosis and how the virus deals with this cellular response. We illustrate a duality in the effects of ZIKV-controlled apoptosis, depending on whether it occurs too early or too late, respectively, in neuropathogenesis, or in long-term viral persistence. We further discuss a prospective role for apoptosis in ZIKV-related therapies, and the use of ZIKV as an oncolytic agent.
MeSH term(s)	Animals ; Antiviral Agents/therapeutic use ; Apoptosis/physiology ; Cell Death/physiology ; Host-Pathogen Interactions/immunology ; Humans ; Immunity, Innate/immunology ; Interferons/therapeutic use ; Microcephaly/virology ; Virus Physiological Phenomena/immunology ; Virus Replication/physiology ; Zika Virus/genetics ; Zika Virus/pathogenicity ; Zika Virus/physiology ; Zika Virus Infection/metabolism ; Zika Virus Infection/virology
Chemical Substances	Antiviral Agents ; Interferons (9008-11-1)
Language	English
Publishing date	2022-01-24
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23031287
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Article: Distribution of Adiponectin Receptors in the Brain of Adult Mouse: Effect of a Single Dose of the Adiponectin Receptor Agonist, AdipoRON, on Ischemic Stroke.

Clain, Julien / Couret, David / Planesse, Cynthia / Krejbich-Trotot, Pascale / Meilhac, Olivier / Lefebvre d'Hellencourt, Christian / Viranaicken, Wildriss / Diotel, Nicolas

Brain sciences

2022 Volume 12, Issue 5

Abstract: Adiponectin exhibits pleiotropic effects, including anti-inflammatory, anti-apoptotic, anti-oxidant, and neuroprotective ones. Although some studies have documented brain expression in different rodent models of its receptors, AdipoR1 and AdipoR2, their ... ...

Abstract	Adiponectin exhibits pleiotropic effects, including anti-inflammatory, anti-apoptotic, anti-oxidant, and neuroprotective ones. Although some studies have documented brain expression in different rodent models of its receptors, AdipoR1 and AdipoR2, their global distribution remains incomplete. Here, we demonstrated that both AdipoR are widely distributed in the brains of adult mice. Furthermore, by double immunostaining studies, we showed that AdipoR1 and AdipoR2 are mainly expressed in neurons and blood vessels. Then, considering the wide distribution of both receptors and the neuroprotective effects of adiponectin, we tested the therapeutic effect of a single injection of the adiponectin receptor agonist, AdipoRON (5 mg.kg
Language	English
Publishing date	2022-05-23
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2651993-8
ISSN	2076-3425
ISSN	2076-3425
DOI	10.3390/brainsci12050680
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