Primate-specific BTN3A2 protects against SARS-CoV-2 infection by interacting with and reducing ACE2 DOI Open Access
Ling Xu, Dandan Yu, Min Xu

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Янв. 15, 2024

Summary Background Coronavirus disease 2019 (COVID-19) is an immune-related disorder caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The complete pathogenesis of the virus remains to be determined. Unraveling molecular mechanisms governing SARS-CoV-2 interactions with host cells crucial for formulation effective prophylactic measures and advancement COVID-19 therapeutics. Methods We analyzed human lung single-cell RNA sequencing dataset discern association butyrophilin subfamily 3 member A2 ( BTN3A2 ) expression COVID-19. gene edited cell lines transgenic mice were infected live in a biosafety level (BSL-3) laboratory. Immunoprecipitation, flow cytometry, biolayer interferometry competition ELISA assays performed cells. quantitative real-time PCR, histological and/or immunohistochemical analyses tissue samples from or without infection. Findings mRNA was correlated severity. predominantly identified epithelial cells, elevated pathological patients co-occurred ACE2 same subtypes. targeted early stage viral life cycle inhibiting attachment through receptor-binding domain (RBD) Spike protein ACE2. inhibited ACE2-mediated infection reducing vitro vivo . Interpretation These results reveal key role fight against Identifying potential monoclonal antibodies which mimic may facilitate disruption infection, providing therapeutic avenue Funding This study supported National Natural Science Foundation China (32070569, U1902215, 32371017), CAS “Light West China” Program, Yunnan Province (202305AH340006). Research context Evidence before this Our understanding COVID-19, especially events incompletely albeit we witnessed many progresses. knowledge gap hinders finding specific antiviral agents SARS-CoV-2. entry mediated receptor angiotensin-converting enzyme (ACE2) affected defenses. Targeting these universal factors required replication most promising approach prevention treatment Added value revealed that BTN3A2, primate-specific gene, acts as potent inhibitor up-regulation upon competed binding protein, subsequently entry. Implications all available evidence data highlighted novel factor protective effects holds considerable drug mitigating impact its variants concern (VOCs).

Язык: Английский

Kynurenine-AhR reduces T-cell infiltration and induces a delayed T-cell immune response by suppressing the STAT1-CXCL9/CXCL10 axis in tuberculosis DOI Creative Commons
Xin Liu,

Mengjie Yang,

Ping Xu

и другие.

Cellular and Molecular Immunology, Год журнала: 2024, Номер unknown

Опубликована: Окт. 22, 2024

Abstract Tuberculosis, caused by Mycobacterium tuberculosis (Mtb), is a critical global health issue that complicated the ability of pathogen to delay host’s T-cell immune response. This in recruitment site infection pivotal survival strategy for Mtb, allowing it establish persistent chronic infection. To investigate underlying mechanisms, this study focused on Mtb’s exploitation host tryptophan metabolism. Mtb upregulates indoleamine 2,3-dioxygenase 1 (IDO1) inflammatory macrophages, thereby increasing kynurenine (Kyn) production. Kyn then activates aryl hydrocarbon receptor (AhR), leading upregulation suppressor cytokine signaling 3 and subsequent inhibition JAK-STAT1 pathway. results reduced secretion chemokines CXCL9 CXCL10, which are crucial lungs. Supported vivo mouse models, our findings reveal disrupting pathway through AhR knockout significantly enhances infiltration activity, undermining Mtb-induced immunosuppression. In contrast, additional injection obviously inhibited activity. These highlight potential therapeutic targets IDO1, offering new avenues enhancing response against guiding future vaccine development efforts.

Язык: Английский

Процитировано

4
Betacoronaviruses SARS-CoV-2 and HCoV-OC43 infections in IGROV-1 cell line require aryl hydrocarbon receptor DOI Creative Commons
Meisam Yousefi,

Wai Suet Lee,

Wharton O. Y. Chan

и другие.

Emerging Microbes & Infections, Год журнала: 2023, Номер 12(2)

Опубликована: Сен. 6, 2023

The emergence of novel betacoronaviruses has posed significant financial and human health burdens, necessitating the development appropriate tools to combat future outbreaks. In this study, we have characterized a cell line, IGROV-1, as robust tool detect, propagate, titrate SARS-CoV-2 HCoV-OC43. IGROV-1 cells can be used for serological assays, antiviral drug testing, isolating variants from patient samples. Using time-course transcriptomics, confirmed that exhibit innate immune response upon infection, recapitulating previously observed in primary nasal epithelial cells. We performed genome-wide CRISPR knockout genetic screens identified Aryl hydrocarbon receptor (AHR) critical host dependency factor both DiMNF, small molecule inhibitor AHR, selectively inhibits HCoV-OC43 infection but not SARS-CoV-2. Transcriptomic analysis normal bronchial revealed DiMNF blocks via basal activation responses. Our findings highlight potential valuable diagnostic research betacoronavirus diseases.

Язык: Английский

Процитировано

9
Punicalagin as a novel selective aryl hydrocarbon receptor (AhR) modulator upregulates AhR expression through the PDK1/p90RSK/AP-1 pathway to promote the anti-inflammatory response and bactericidal activity of macrophages DOI Creative Commons

Weihong Dai,

Shuangqin Yin,

Fangjie Wang

и другие.

Cell Communication and Signaling, Год журнала: 2024, Номер 22(1)

Опубликована: Окт. 3, 2024

Язык: Английский

Процитировано

3
Decoding structural determinants of aryl hydrocarbon receptor antagonism by monoterpenoids DOI
Iveta Zůvalová, Barbora Vyhlídalová, Karolína Ondrová

и другие.

Bioorganic Chemistry, Год журнала: 2025, Номер 157, С. 108265 - 108265

Опубликована: Фев. 10, 2025

Язык: Английский

Процитировано

0
Potential role for kynurenine pathway in increased COVID-19 mortality of patients with schizophrenia DOI
Pengli Wang,

Zhen-Ying Li,

Jie Wang

и другие.

Journal of Psychiatric Research, Год журнала: 2025, Номер 183, С. 289 - 295

Опубликована: Фев. 21, 2025

Язык: Английский

Процитировано

0
Insight into the Role of the Aryl Hydrocarbon Receptor in Bovine Coronavirus Infection by an Integrated Approach Combining In Vitro and In Silico Methods DOI Creative Commons

Luca Del Sorbo,

Clementina Acconcia, Maria Michela Salvatore

и другие.

Microorganisms, Год журнала: 2025, Номер 13(3), С. 579 - 579

Опубликована: Март 4, 2025

It is well known that the host response to different human and animal coronaviruses infection regulated by aryl hydrocarbon receptor, a ligand-activated transcription factor. The present study investigates expression of receptor during bovine coronavirus infection, through in vitro silico investigations. studies demonstrate as its targets, CYP1A1 CYP1B1, were significantly activated cells (MDBK). During pretreatment with non-cytotoxic doses CH223191, selective inhibitor resulted significant reduction virus yield downregulation viral spike protein expression. These findings occurred presence inhibition signaling. Our results reveal acts on replication, upregulating downstream target proteins, CYP1B1. In addition, following studies, three-dimensional structural model complex antagonist CH223191 indicates molecular mechanism, which PASB TAD domains interact inhibitor, mainly driven an extensive network hydrophobic interactions, series hydrogen bonds contributing stabilizing complex. Interestingly, bioinformatic analyses revealed high similarity at primary sequence structure levels. Taken together, these represent fundamental step for development innovative drugs targeting AhR potential object CoVs therapy.

Язык: Английский

Процитировано

0
The role of aryl hydrocarbon receptor in antiviral immunity: a focus on RNA viruses DOI Creative Commons
Aneta Grycová, Barbora Vyhlídalová, Zdeněk Dvořák

и другие.

Critical Reviews in Microbiology, Год журнала: 2025, Номер unknown, С. 1 - 15

Опубликована: Апрель 29, 2025

Aryl hydrocarbon receptor (AhR) is a ligand-dependent transcriptional factor that activated by plethora of exogenous and endogenous compounds, including environmental pollutants, drugs, microbial metabolites. The AhR plays an important role in modulating immunity. Current findings suggest activation serves as mechanism for evasion host antiviral immune response promotes viral replication. This review will focus on AhR's RNA virus infection because they show high mutation rates compared with DNA viruses, therefo pose one the greatest threats to humans terms potential pandemic risk. Indeed, include human immunodeficiency (HIV), influenza A (IAV), coronaviruses (CoVs), Zika virus, others. Understanding mechanisms which influences these viruses critical developing effective therapeutic strategies. By focusing interplay between signaling infections, this aims contribute growing body knowledge regarding host-pathogen interactions implications

Язык: Английский

Процитировано

0
Long Neuro-COVID-19: Current Mechanistic Views and Therapeutic Perspectives DOI Creative Commons
Anny Slama‐Schwok, Julien Henri

Biomolecules, Год журнала: 2024, Номер 14(9), С. 1081 - 1081

Опубликована: Авг. 28, 2024

Long-lasting COVID-19 (long COVID) diseases constitute a real life-changing burden for many patients around the globe and, overall, can be considered societal and economic issues. They include variety of symptoms, such as fatigue, loss smell (anosmia), neurological–cognitive sequelae, memory loss, anxiety, brain fog, acute encephalitis, stroke, collectively called long neuro-COVID-19 neuro-COVID). also cardiopulmonary myocardial infarction, pulmonary damage, fibrosis, gastrointestinal dysregulation, renal failure, vascular endothelial onset new diabetes, with each symptom usually being treated individually. The main unmet challenge is to understand mechanisms pathophysiologic in particular neurological symptoms. This mini-review presents mechanistic hypotheses explain multiple neuro-COVID namely immune dysregulation prolonged inflammation, persistent viral reservoirs, dysfunction, disruption neurotransmitter signaling along various paths. We suggest that nucleoprotein N SARS-CoV-2 constitutes “hub” between virus host immunity, neurotransmission.

Язык: Английский

Процитировано

2
A review of virus host factor discovery using CRISPR screening DOI Creative Commons

W. See,

Meisam Yousefi, Yaw Shin Ooi

и другие.

mBio, Год журнала: 2024, Номер 15(11)

Опубликована: Окт. 18, 2024

ABSTRACT The emergence of genome-scale forward genetic screening techniques, such as Haploid Genetic screen and clustered regularly interspaced short palindromic repeats (CRISPR) knockout has opened new horizons in our understanding virus infection biology. CRISPR become a popular tool for the discovery novel host factors several viruses due to its specificity efficiency genome editing. Here, we review how revolutionized virus-host interactions from scientific technological viewpoints. A summary published screens conducted thus far uncover is presented, highlighting their experimental design significant findings. We will outline relevant methods customizing process answer more specific hypotheses compile glossary show aspects. Furthermore, using flaviviruses severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) examples, hope offer broad-based perspective on capabilities serve reference point guide future unbiased factors.

Язык: Английский

Процитировано

2
SARS-CoV-2 S protein disrupts the formation of ISGF3 complex through conserved S2 subunit to antagonize type I interferon response DOI Creative Commons
Zeng Cai, Wenjia Ni, Wenkang Li

и другие.

Journal of Virology, Год журнала: 2024, Номер 99(1)

Опубликована: Дек. 19, 2024

Viral immunosuppression substantially affects the host immune response of infected patients and protective efficacy vaccines. Here, we found that spike (S) protein, major vaccine antigen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), strongly suppresses innate immunity by inhibiting interferon-stimulated gene (ISG) expression through both S1 S2 subunits. Mechanistically, S protein inhibited formation classic factor 3 (ISGF3) complex composed STAT1, STAT2, IRF9 competing with STAT2 for binding to IRF9, thereby impeding transcription ISGs. A strong interaction between STAT1/STAT2 proteins further traps ISGF3 in endoplasmic reticulum hinders nuclear translocation ISGF3. Notably, interferon-inhibitory mechanism was universal among SARS-CoV-2 variants other human coronaviruses, including SARS-CoV, Middle East (MERS-CoV), 229E (HCoV-229E), NL63 (HCoV-NL63), HKU1 (HCoV-HKU1), most evolutionarily conserved region subunit. Taken together, findings this study reveal a new which attenuates antiviral provides insights into proper design S-based vaccines prevent immunosuppressive effects. This unveils (SARS-CoV-2) host's response. The MERS-CoV, HCoV-229E, HCoV-NL63, HCoV-HKU1, domains. Our expands understanding coronaviruses evading strategies, is very important optimization antigens, thus providing theoretical basis anti-coronavirus coronavirus.

Язык: Английский

Процитировано

2