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Article ; Online: Possible contribution of rare alleles of human ACE2 in the emergence of SARS-CoV-2 variants escaping the immune response.

Devaux, Christian A / Fantini, Jacques

2023 Volume 14, Page(s) 1252367

Abstract: Since the start of the SARS-CoV-2 pandemic, the rapid replacement of one lineage by another has been observed. Indeed, SARS-CoV-2 is evolving through a quasispecies mechanism leading to post-infection mutation selection under positive evolutionary ... ...

Abstract	Since the start of the SARS-CoV-2 pandemic, the rapid replacement of one lineage by another has been observed. Indeed, SARS-CoV-2 is evolving through a quasispecies mechanism leading to post-infection mutation selection under positive evolutionary pressure (host-driven viral evolution). These mutations may reduce the effectiveness of the specific neutralizing immune response against the virus. We provide here evidence that apart from the selection of SARS-CoV-2 variants by the immune system, selection by the cellular receptor can just as well select variants which escape neutralization.
MeSH term(s)	Humans ; Alleles ; Angiotensin-Converting Enzyme 2/genetics ; COVID-19/immunology ; SARS-CoV-2
Chemical Substances	Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; ACE2 protein, human (EC 3.4.17.23)
Language	English
Publishing date	2023-10-10
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1252367
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Unravelling Antigenic Cross-Reactions toward the World of Coronaviruses: Extent of the Stability of Shared Epitopes and SARS-CoV-2 Anti-Spike Cross-Neutralizing Antibodies.

Devaux, Christian A / Fantini, Jacques

Pathogens (Basel, Switzerland)

2023 Volume 12, Issue 5

Abstract: The human immune repertoire retains the molecular memory of a very great diversity of target antigens (epitopes) and can recall this upon a second encounter with epitopes against which it has previously been primed. Although genetically diverse, proteins ...

Abstract	The human immune repertoire retains the molecular memory of a very great diversity of target antigens (epitopes) and can recall this upon a second encounter with epitopes against which it has previously been primed. Although genetically diverse, proteins of coronaviruses exhibit sufficient conservation to lead to antigenic cross-reactions. In this review, our goal is to question whether pre-existing immunity against seasonal human coronaviruses (HCoVs) or exposure to animal CoVs has influenced the susceptibility of human populations to SARS-CoV-2 and/or had an impact upon the physiopathological outcome of COVID-19. With the hindsight that we now have regarding COVID-19, we conclude that although antigenic cross-reactions between different coronaviruses exist, cross-reactive antibody levels (titers) do not necessarily reflect on memory B cell frequencies and are not always directed against epitopes which confer cross-protection against SARS-CoV-2. Moreover, the immunological memory of these infections is short-term and occurs in only a small percentage of the population. Thus, in contrast to what might be observed in terms of cross-protection at the level of a single individual recently exposed to circulating coronaviruses, a pre-existing immunity against HCoVs or other CoVs can only have a very minor impact on SARS-CoV-2 circulation at the level of human populations.
Language	English
Publishing date	2023-05-13
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2695572-6
ISSN	2076-0817
ISSN	2076-0817
DOI	10.3390/pathogens12050713
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Article: ACE2 receptor polymorphism in humans and animals increases the risk of the emergence of SARS-CoV-2 variants during repeated intra- and inter-species host-switching of the virus.

Devaux, Christian A / Fantini, Jacques

Frontiers in microbiology

2023 Volume 14, Page(s) 1199561

Abstract: Like other coronaviruses, SARS-CoV-2 has ability to spread through human-to-human transmission and to circulate from humans to animals and from animals to humans. A high frequency of SARS-CoV-2 mutations has been observed in the viruses isolated from ... ...

Abstract	Like other coronaviruses, SARS-CoV-2 has ability to spread through human-to-human transmission and to circulate from humans to animals and from animals to humans. A high frequency of SARS-CoV-2 mutations has been observed in the viruses isolated from both humans and animals, suggesting a genetic fitness under positive selection in both ecological niches. The most documented positive selection force driving SARS-CoV-2 mutations is the host-specific immune response. However, after electrostatic interactions with lipid rafts, the first contact between the virus and host proteins is the viral spike-cellular receptor binding. Therefore, it is likely that the first level of selection pressure impacting viral fitness relates to the virus's affinity for its receptor, the angiotensin I converting enzyme 2 (ACE2). Although sufficiently conserved in a huge number of species to support binding of the viral spike with enough affinity to initiate fusion, ACE2 is highly polymorphic both among species and within a species. Here, we provide evidence suggesting that when the viral spike-ACE2 receptor interaction is not optimal, due to host-switching, mutations can be selected to improve the affinity of the spike for the ACE2 expressed by the new host. Notably, SARS-CoV-2 is mutation-prone in the spike receptor binding domain (RBD), allowing a better fit for ACE2 orthologs in animals. It is possibly that this may also be true for rare human alleles of ACE2 when the virus is spreading to billions of people. In this study, we present evidence that human subjects expressing the rare E
Language	English
Publishing date	2023-07-13
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587354-4
ISSN	1664-302X
ISSN	1664-302X
DOI	10.3389/fmicb.2023.1199561
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Article ; Online: Molecular Mimicry of the Viral Spike in the SARS-CoV-2 Vaccine Possibly Triggers Transient Dysregulation of ACE2, Leading to Vascular and Coagulation Dysfunction Similar to SARS-CoV-2 Infection.

Devaux, Christian A / Camoin-Jau, Laurence

Viruses

2023 Volume 15, Issue 5

Abstract: The benefits of SARS-CoV-2 spike mRNA vaccines are well known, including a significant decline in COVID-19 morbidity and a decrease in the mortality rate of SARS-CoV-2 infected persons. However, pharmacovigilance studies have revealed the existence of ... ...

Abstract	The benefits of SARS-CoV-2 spike mRNA vaccines are well known, including a significant decline in COVID-19 morbidity and a decrease in the mortality rate of SARS-CoV-2 infected persons. However, pharmacovigilance studies have revealed the existence of rare cases of cardiovascular complications after mass vaccination using such formulations. Cases of high blood pressure have also been reported but were rarely documented under perfectly controlled medical supervision. The press release of these warning signals triggered a huge debate over COVID-19 vaccines' safety. Thereby, our attention was quickly focused on issues involving the risk of myocarditis, acute coronary syndrome, hypertension and thrombosis. Rare cases of undesirable post-vaccine pathophysiological phenomena should question us, especially when they occur in young subjects. They are more likely to occur with inappropriate use of mRNA vaccine (e.g., at the time when the immune response is already very active during a low-noise infection in the process of healing), leading to angiotensin II (Ang II) induced inflammation triggering tissue damage. Such harmful effects observed after the COVID-19 vaccine evoke a possible molecular mimicry of the viral spike transiently dysregulating angiotensin converting enzyme 2 (ACE2) function. Although the benefit/risk ratio of SARS-CoV-2 spike mRNA vaccine is very favorable, it seems reasonable to suggest medical surveillance to patients with a history of cardiovascular diseases who receive the COVID-19 vaccine.
MeSH term(s)	Humans ; COVID-19/prevention & control ; COVID-19 Vaccines/adverse effects ; SARS-CoV-2/metabolism ; Angiotensin-Converting Enzyme 2/genetics ; Renin-Angiotensin System/physiology ; Peptidyl-Dipeptidase A/metabolism ; Molecular Mimicry ; Hypertension ; Blood Coagulation Disorders ; Spike Glycoprotein, Coronavirus/genetics ; Spike Glycoprotein, Coronavirus/metabolism
Chemical Substances	COVID-19 Vaccines ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; Peptidyl-Dipeptidase A (EC 3.4.15.1) ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2
Language	English
Publishing date	2023-04-25
Publishing country	Switzerland
Document type	Journal Article ; Review ; 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/v15051045
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Article ; Online: Is it time to switch to a formulation other than the live attenuated poliovirus vaccine to prevent poliomyelitis?

Devaux, Christian Albert / Pontarotti, Pierre / Levasseur, Anthony / Colson, Philippe / Raoult, Didier

Frontiers in public health

2024 Volume 11, Page(s) 1284337

Abstract: The polioviruses (PVs) are mainly transmitted by direct contact with an infected person through the fecal-oral route and respiratory secretions (or more rarely via contaminated water or food) and have a primary tropism for the gut. After their ... ...

Abstract	The polioviruses (PVs) are mainly transmitted by direct contact with an infected person through the fecal-oral route and respiratory secretions (or more rarely via contaminated water or food) and have a primary tropism for the gut. After their replication in the gut, in rare cases (far less than 1% of the infected individuals), PVs can spread to the central nervous system leading to flaccid paralysis, which can result in respiratory paralysis and death. By the middle of the 20th century, every year the wild polioviruses (WPVs) are supposed to have killed or paralyzed over half a million people. The introduction of the oral poliovirus vaccines (OPVs) through mass vaccination campaigns (combined with better application of hygiene measures), was a success story which enabled the World Health Organization (WHO) to set the global eradication of poliomyelitis as an objective. However this strategy of viral eradication has its limits as the majority of poliomyelitis cases today arise in individuals infected with circulating vaccine-derived polioviruses (cVDPVs) which regain pathogenicity following reversion or recombination. In recent years (between January 2018 and May 2023), the WHO recorded 8.8 times more cases of polio which were linked to the attenuated OPV vaccines (3,442 polio cases after reversion or recombination events) than cases linked to a WPV (390 cases). Recent knowledge of the evolution of RNA viruses and the exchange of genetic material among biological entities of the intestinal microbiota, call for a reassessment of the polio eradication vaccine strategies.
MeSH term(s)	Humans ; Poliomyelitis/prevention & control ; Central Nervous System ; Behavior Therapy ; Poliovirus Vaccines ; Vaccines
Chemical Substances	Poliovirus Vaccines ; Vaccines
Language	English
Publishing date	2024-01-08
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2711781-9
ISSN	2296-2565 ; 2296-2565
ISSN (online)	2296-2565
ISSN	2296-2565
DOI	10.3389/fpubh.2023.1284337
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Article: An update on angiotensin-converting enzyme 2 structure/functions, polymorphism, and duplicitous nature in the pathophysiology of coronavirus disease 2019: Implications for vascular and coagulation disease associated with severe acute respiratory syndrome coronavirus infection.

Devaux, Christian A / Camoin-Jau, Laurence

Frontiers in microbiology

2022 Volume 13, Page(s) 1042200

Abstract: It has been known for many years that the angiotensin-converting enzyme 2 (ACE2) is a cell surface enzyme involved in the regulation of blood pressure. More recently, it was proven that the severe acute respiratory syndrome coronavirus (SARS-CoV-2) ... ...

Abstract	It has been known for many years that the angiotensin-converting enzyme 2 (ACE2) is a cell surface enzyme involved in the regulation of blood pressure. More recently, it was proven that the severe acute respiratory syndrome coronavirus (SARS-CoV-2) interacts with ACE2 to enter susceptible human cells. This functional duality of ACE2 tends to explain why this molecule plays such an important role in the clinical manifestations of coronavirus disease 2019 (COVID-19). At the very start of the pandemic, a publication from our Institute (entitled "ACE2 receptor polymorphism: susceptibility to SARS-CoV-2, hypertension, multi-organ failure, and COVID-19 disease outcome"), was one of the first reviews linking COVID-19 to the duplicitous nature of ACE2. However, even given that COVID-19 pathophysiology may be driven by an imbalance in the renin-angiotensin system (RAS), we were still far from understanding the complexity of the mechanisms which are controlled by ACE2 in different cell types. To gain insight into the physiopathology of SARS-CoV-2 infection, it is essential to consider the polymorphism and expression levels of the
Language	English
Publishing date	2022-11-28
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2587354-4
ISSN	1664-302X
ISSN	1664-302X
DOI	10.3389/fmicb.2022.1042200
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Article ; Online: Le virus SARS-CoV-2 n’a pas « d’origine ».

Frutos, Roger / Gavotte, Laurent / Devaux, Christian A

Medecine sciences : M/S

2022 Volume 38, Issue 6-7, Page(s) 600–607

Abstract: Since the beginning of the COVID-19 pandemic, the question of the origin of this virus has been the subject of a vivid controversy. It is the question of the "origin" itself which is biased. Darwin showed that there is no determined origin to any animal ... ...

Title translation	SARS-CoV-2 has no origin.
Abstract	Since the beginning of the COVID-19 pandemic, the question of the origin of this virus has been the subject of a vivid controversy. It is the question of the "origin" itself which is biased. Darwin showed that there is no determined origin to any animal or plant species, simply an evolutionary and selective process. The same is true for viruses, there is no origin, but an evolutionary process. Viruses circulate from host to host, animals or humans. Pandemic viruses are already circulating in humans and evolving before the onset of disease. This evolutionary process then continues and gives rise to successive variants. The solution is not to target the disease or the putative causative agent but rather to address the process of disease emergence.
MeSH term(s)	Animals ; COVID-19 ; Humans ; Pandemics ; SARS-CoV-2
Language	French
Publishing date	2022-06-29
Publishing country	France
Document type	Journal Article
ZDB-ID	632733-3
ISSN	1958-5381 ; 0767-0974
ISSN (online)	1958-5381
ISSN	0767-0974
DOI	10.1051/medsci/2022079
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Unraveling the Underlying Molecular Mechanism of 'Silent Hypoxia' in COVID-19 Patients Suggests a Central Role for Angiotensin II Modulation of the AT1R-Hypoxia-Inducible Factor Signaling Pathway.

Devaux, Christian Albert / Lagier, Jean-Christophe

Journal of clinical medicine

2023 Volume 12, Issue 6

Abstract: A few days after being infected with SARS-CoV-2, a fraction of people remain asymptomatic but suffer from a decrease in arterial oxygen saturation in the absence of apparent dyspnea. In light of our clinical investigation on the modulation of molecules ... ...

Abstract	A few days after being infected with SARS-CoV-2, a fraction of people remain asymptomatic but suffer from a decrease in arterial oxygen saturation in the absence of apparent dyspnea. In light of our clinical investigation on the modulation of molecules belonging to the renin angiotensin system (RAS) in COVID-19 patients, we propose a model that explains 'silent hypoxia'. The RAS imbalance caused by SARS-CoV-2 results in an accumulation of angiotensin 2 (Ang II), which activates the angiotensin 2 type 1 receptor (AT1R) and triggers a harmful cascade of intracellular signals leading to the nuclear translocation of the hypoxia-inducible factor (HIF)-1α. HIF-1α transactivates many genes including the angiotensin-converting enzyme 1 (ACE1), while at the same time, ACE2 is downregulated. A growing number of cells is maintained in a hypoxic condition that is self-sustained by the presence of the virus and the ACE1/ACE2 ratio imbalance. This is associated with a progressive worsening of the patient's biological parameters including decreased oxygen saturation, without further clinical manifestations. When too many cells activate the Ang II-AT1R-HIF-1α axis, there is a 'hypoxic spillover', which marks the tipping point between 'silent' and symptomatic hypoxia in the patient. Immediate ventilation is required to prevent the 'hypoxic spillover'.
Language	English
Publishing date	2023-03-22
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm12062445
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Article ; Online: Editorial: Dynamic of Transmissible Diseases: Integrative and Transdisciplinary Approaches.

Frutos, Roger / Gavotte, Laurent / Serra-Cobo, Jordi / Devaux, Christian A

Frontiers in public health

2022 Volume 10, Page(s) 862069

MeSH term(s)	Communicable Diseases ; Humans ; Patient Care Team
Language	English
Publishing date	2022-02-24
Publishing country	Switzerland
Document type	Editorial ; Introductory Journal Article
ZDB-ID	2711781-9
ISSN	2296-2565 ; 2296-2565
ISSN (online)	2296-2565
ISSN	2296-2565
DOI	10.3389/fpubh.2022.862069
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Article ; Online: Identification and Characterization of an HtrA Sheddase Produced by

Osman, Ikram Omar / Caputo, Aurelia / Pinault, Lucile / Mege, Jean-Louis / Levasseur, Anthony / Devaux, Christian A

International journal of molecular sciences

2023 Volume 24, Issue 13

Abstract: Having previously shown that soluble E-cadherin (sE-cad) is found in sera of Q fever patients and that infection of BeWo cells ... ...

Abstract	Having previously shown that soluble E-cadherin (sE-cad) is found in sera of Q fever patients and that infection of BeWo cells by
MeSH term(s)	Humans ; Coxiella burnetii/enzymology ; Coxiella burnetii/genetics ; Coxiella burnetii/pathogenicity ; Interleukin-10/metabolism ; Macrophages/microbiology ; Q Fever/microbiology ; Q Fever/physiopathology ; THP-1 Cells/microbiology ; Cadherins/metabolism ; Genome, Bacterial/genetics ; Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; Gene Expression Regulation, Bacterial ; Recombinant Proteins/genetics ; Host Microbial Interactions ; Serine Endopeptidases/genetics ; Serine Endopeptidases/metabolism ; Escherichia coli/genetics
Chemical Substances	Interleukin-10 (130068-27-8) ; DegP protease (EC 3.4.21.-) ; Cadherins ; Bacterial Proteins ; Recombinant Proteins ; Serine Endopeptidases (EC 3.4.21.-)
Language	English
Publishing date	2023-06-30
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms241310904
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