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

In Vitro Evaluation of Aryl Hydrocarbon Receptor Involvement in Feline Coronavirus Infection DOI Creative Commons

Luca Del Sorbo,

Rosa Giugliano,

Claudia Cerracchio

и другие.

Viruses, Год журнала: 2025, Номер 17(2), С. 227 - 227

Опубликована: Фев. 6, 2025

Feline coronavirus (FCoV) is an alphacoronavirus (αCoV) that causes moderate or chronic asymptomatic infection in cats. However, a single infected cat, FCoV can modify its cellular tropism by acquiring the ability to infect macrophages, resulting development of feline infectious peritonitis (FIP). In this context, restrain impact infection, scientific research has focused attention on antiviral therapies involving novel mechanisms action. Recent studies have demonstrated aryl hydrocarbon receptor (AhR) signaling regulates host response different human and animal CoVs. Hence, mechanism action AhR was evaluated upon Crandell Kidney (CRFK) canine fibrosarcoma (A72) cells. Following with enteric CoV (FECV), strain "München", significant activation target CYP1A1, observed. The selective antagonist CH223191 provoked reduction replication levels viral nucleocapsid protein (NP). Furthermore, effect inhibitor acidity lysosomes cells Our findings indicate acts upregulates AhR. repressed virus yield through inhibition respect, for counteracting FCoV, represents new useful identifying drugs. Moreover, presence CH223191, alkalinization FCoV-infected CRFK detected, outlining their involvement activity.

Язык: Английский

Процитировано

1
Canine coronavirus infection is intensified by 2,3,7,8-tetrachlorodibenzo-p-dioxin DOI Creative Commons

Luca Del Sorbo,

Claudia Cerracchio,

Francesco Serra

и другие.

Archives of Toxicology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 22, 2025

Abstract In humans as well in animals, the toxic contaminant 2,3,7,8-tetrachlorodibenzo- p- dioxin (TCDD) stimulates immunosuppression and increases responsiveness to infectious diseases. The relationship between environmental contaminants different diseases, including COVID-19, has been described. Nevertheless, reports about potential impact of TCDD on coronaviruses (CoVs) are limited. this study, (0–100 pg/mL) was assessed during infection vitro with canine coronavirus (CCoV-II), alphaCoV causing moderate enteric disease dogs, although genetic alterations may surprisingly generate new dangerous strains. For instance, outbreaks lethal infections dogs were related highly virulent CCoV strains, cases pneumonia malaise associated canine–feline recombinant strains CCoV, underlining cross-species spread capability CoVs. Herein, infection, induced a substantial growth virus yield expression viral nucleocapsid protein infected groups. Infected cells exhibited cell morphology, extensively enhanced by TCDD. Moreover, modulated levels aryl hydrocarbon receptor (AHR), signaling responsive both CoVs infections. Overall, our findings showed that TCDD, playing role AHR signaling, worsen infection.

Язык: Английский

Процитировано

1
Hydrogen-rich water alleviates asthma airway inflammation by modulating tryptophan metabolism and activating aryl hydrocarbon receptor via gut microbiota regulation DOI
Li Li Li, Ziqian Xu,

Haoran Ni

и другие.

Free Radical Biology and Medicine, Год журнала: 2024, Номер 224, С. 50 - 61

Опубликована: Авг. 13, 2024

Язык: Английский

Процитировано

8
The role of the AHR in host–pathogen interactions DOI
Palmira Barreira‐Silva, Yilong Lian, Stefan H. E. Kaufmann

и другие.

Nature reviews. Immunology, Год журнала: 2024, Номер unknown

Опубликована: Окт. 16, 2024

Язык: Английский

Процитировано

8
Fungal metabolite 6-pentyl-α-pyrone reduces canine coronavirus infection DOI Creative Commons

Claudia Cerracchio,

Luca Del Sorbo,

Francesco Serra

и другие.

Heliyon, Год журнала: 2024, Номер 10(6), С. e28351 - e28351

Опубликована: Март 1, 2024

Canine coronavirus (CCoV) can produce a self-limited enteric disease in dogs but, because of notable biological plasticity coronaviruses (CoVs), numerous mutations as well recombination events happen leading to the emergence variants often more dangerous for both animals and humans. Indeed, new canine-feline recombinant alphacoronaviruses, recently isolated from humans, highlight cross-species transmission potential CoVs. Consequently, effective antiviral agents are required treat CoV infections. Among candidates development drugs against CoVs infection, fungal secondary metabolites (SMs) represent an important source investigate. Herein, ability 6-pentyl-α-pyrone (6 PP), SM obtained by

Язык: Английский

Процитировано

6
Role of aryl hydrocarbon receptors in infection and inflammation DOI Creative Commons

Linglan Xu,

Luping Lin,

Nan Xie

и другие.

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Апрель 12, 2024

The aryl hydrocarbon receptor (AhR) is a transcription factor that activated by various ligands, including pollutants, microorganisms, and metabolic substances. It expressed extensively in pulmonary intestinal epithelial cells, where it contributes to barrier defense. expression of AhR pivotal regulating the inflammatory response microorganisms. However, dysregulated can result endocrine disorders, leading immunotoxicity potentially promoting development carcinoma. This review focuses on crucial role facilitating limiting proliferation pathogens, specifically relation host cell type species etiological agents involved microbial pathogen infections. activation enhanced through IDO1-AhR-IDO1 positive feedback loop, which manipulated viruses. primarily promotes infection SARS-CoV-2 inducing angiotensin-converting enzyme 2 (ACE2) secretion pro-inflammatory cytokines. also plays significant types T-cells, CD4 + T cells CD8 context pathway immune responses within respiratory barriers when they are invaded viruses, bacteria, parasites, fungi. Additionally, we propose targeting agonist antagonist signaling pathways could serve as promising therapeutic approach for combating infections, especially light growing prevalence drug resistance multiple antibiotics.

Язык: Английский

Процитировано

6
Aryl hydrocarbon receptor activation alters immune cell populations in the lung and bone marrow during coronavirus infection DOI Creative Commons

Alicia Marie Healey,

Kristina N. Fenner,

Colleen O’Dell

и другие.

AJP Lung Cellular and Molecular Physiology, Год журнала: 2024, Номер 326(3), С. L313 - L329

Опубликована: Янв. 30, 2024

Respiratory viral infections are one of the major causes illness and death worldwide. Symptoms associated with respiratory can range from mild to severe, there is limited understanding why large variation in severity. Environmental exposures a potential causative factor. The aryl hydrocarbon receptor (AHR) an environment-sensing molecule expressed all immune cells. Although considerable evidence that AHR signaling influences responses other challenges, including pathogens, less known about impact on during coronavirus (CoV) infection. In this study, we report activation significantly altered cells lungs bone marrow mice infected mouse CoV. transiently reduced frequency multiple mononuclear phagocyte system, monocytes, interstitial macrophages, dendritic lung. marrow, myelopoiesis, as evidenced by reduction granulocyte-monocyte progenitor increased myeloid-biased Moreover, affected stages megakaryocyte lineage. Overall, these findings indicate modulates aspects response CoV Given significant burden viruses human health, how environmental shape infection advances our knowledge factors contribute variability disease severity provides insight into novel approaches prevent or treat disease.

Язык: Английский

Процитировано

5
Modulatory Roles of AHR, FFAR2, FXR, and TGR5 Gene Expression in Metabolic-Associated Fatty Liver Disease and COVID-19 Outcomes DOI Creative Commons
Mykhailo Buchynskyi, Valentyn Oksenych, Iryna Kamyshna

и другие.

Viruses, Год журнала: 2024, Номер 16(6), С. 985 - 985

Опубликована: Июнь 19, 2024

Metabolic-associated fatty liver disease (MAFLD) is a risk factor for severe COVID-19. This study explores the potential influence of gut hormone receptor and immune response gene expression on COVID-19 outcomes in MAFLD patients.

Язык: Английский

Процитировано

5
Host factors of SARS-CoV-2 in infection, pathogenesis, and long-term effects DOI Creative Commons

Yu Zhang,

Shihan Chen, Yan Tian

и другие.

Frontiers in Cellular and Infection Microbiology, Год журнала: 2024, Номер 14

Опубликована: Май 22, 2024

SARS-CoV-2 is the causative virus of devastating COVID-19 pandemic that results in an unparalleled global health and economic crisis. Despite unprecedented scientific efforts therapeutic interventions, fight against continues as rapid emergence different variants concern increasing challenge long COVID-19, raising a vast demand to understand pathomechanisms its long-term sequelae develop strategies beyond per se . Notably, addition itself, replication cycle clinical severity also governed by host factors. In this review, we therefore comprehensively overview pathogenesis from perspective factors host-virus interactions. We sequentially outline pathological implications molecular interactions between multi-organ multi-system summarize current agents targeting for treating these diseases. This knowledge would be key identification new pathophysiological aspects mechanisms, development actionable targets tackling sequelae.

Язык: Английский

Процитировано

4
Tryptophan As a New Member of RNA‐Induced Silencing Complexes Prevents Colon Cancer Liver Metastasis DOI Creative Commons
Fangyi Xu, Yi Ren,

Yun Teng

и другие.

Advanced Science, Год журнала: 2024, Номер 11(31)

Опубликована: Июнь 20, 2024

Abstract Essential amino acids (EAA) and microRNAs (miRs) control biological activity of a cell. Whether EAA regulates the miR has never been demonstrated. Here, as proof‐of‐concept, tryptophan (Trp, an EAA) complex containing Argonaute 2 (Ago2) miRs including miR‐193a (Trp/Ago2/miR‐193a) is identified. Trp binds miR‐193a‐3p interacts with Ago2. Trp/Ago2/miR‐193a increases via enhancing RNase activity. Other miR‐103 miR‐107 in enhance by targeting same genes. Mechanistically, Trp‐binding pockets PIWI domain Ago2 to mediated This newly formed Ago2/Trp/miR‐193a‐3p more efficient than alone inhibiting expression targeted genes colon cancer liver metastasis. The findings show that through communication RNA‐induced silencing complexes (RISC), which provides basis for based therapy.

Язык: Английский

Процитировано

4