Journal of Medical Virology, Год журнала: 2025, Номер 97(1)
Опубликована: Янв. 1, 2025
ABSTRACT SARS‐CoV‐2 Envelope (E) protein is critical in viral assembly, release, and virulence. E gene was considered highly conserved evolving slowly. Pan‐sarbecoviruses–conserved regions the have been used as targets for various RT‐PCR assays to detect SARS‐CoV‐2. It remains elusive whether variants of concern (VOCs) accumulated significant mutations that may affect stability diagnostic assays. Herein we aimed perform a comprehensive genetic analysis on conservation diversity its VOCs comparison with other human coronaviruses (HCoVs). In silico 20 326 HCoV sequences retrieved from GenBank GISAID suggests has multiple pan‐HCoVs– pan‐SARS‐CoV‐2–conserved positions but accumulates VOC B.1.351 Omicron strains. Mutations were often found 5′ 3′ variable regions, whereas central region conserved. Nucleotide changes C109U A114G lead potential failure first‐line diagnostic/screening change C212U concomitant amino acid substitution Pro71Leu (i.e., C212U/Pro71Leu) hallmark mutation variants, while C26U/Thr9Ile characteristic all variants. Later subvariants, such XBB.1.5 EG.5, additionally acquired A31G/Thr11Ala mutation, confirmed by whole genome sequencing 118 pediatric cases. Wild‐type exhibits cytotoxicity cells, Thr9Ile, Thr11Ala, Thr9Ile + or reduces cytotoxicity. The Thr11Ala stabilizes proteins alters cellular distribution protein, reducing colocalization Golgi body. Altogether, this study not only sheds light also informs improvement development pan‐HCoVs screening
Язык: Английский
Процитировано
6The Immunopathogenesis of a Cytokine Storm: The Key Mechanisms Underlying Severe COVID-19
Cytokine & Growth Factor Reviews, Год журнала: 2025, Номер unknown
Опубликована: Янв. 1, 2025
A cytokine storm is marked by excessive pro-inflammatory release, and has emerged as a key factor in severe COVID-19 cases - making it critical therapeutic target. However, its pathophysiology was poorly understood, which hindered effective treatment. SARS-CoV-2 initially disrupts angiotensin signalling, promoting inflammation through ACE-2 downregulation. Some patients' immune systems then fail to shift from innate adaptive immunity, suppressing interferon responses leading pyroptosis neutrophil activation. This amplifies tissue damage inflammation, creating loop. The result the disruption of Th1/Th2 Th17/Treg balances, lymphocyte exhaustion, extensive blood clotting. Cytokine treatments include glucocorticoids suppress system, monoclonal antibodies neutralize specific cytokines, JAK inhibitors block receptor signalling. most treatment options for mitigating infection remain vaccines preventive measure antiviral drugs early stages infection. article synthesizes insights into dysregulation COVID-19, offering framework better understand storms improve monitoring, biomarker discovery, strategies other conditions involving storms.
Язык: Английский
Процитировано
6SARS‐CoV‐2 Productively Infects Human Hepatocytes and Induces Cell Death
Journal of Medical Virology, Год журнала: 2025, Номер 97(1)
Опубликована: Янв. 1, 2025
SARS-CoV-2 infection is accompanied by elevated liver enzymes, and patients with pre-existing conditions experience more severe disease. While it was known that infects human hepatocytes, our study determines the mechanism of infection, demonstrates viral replication spread, highlights direct hepatocyte damage. Viral readily detectable upon primary hepatocytes hepatoma cells ancestral SARS-CoV-2, Delta, Omicron variants. Hepatocytes express receptor ACE2 host cell protease TMPRSS2, knocking down TMPRSS2 impaired infection. Progeny viruses released from infected showed typical coronavirus morphology electron microscopy proved infectious when transferred to fresh cells, indicating can contribute virus spread. Importantly, rapidly induced death in a replication-dependent fashion, variant showing faster onset but less extensive death. C57BL/6 wild-type mice mouse-adapted strain high levels RNA lung tissues. ALT peaked cleared liver. Liver histology revealed profound tissue damage immune infiltration, cytopathic effects immune-mediated killing pathology.
Язык: Английский
Процитировано
1Pathogenesis of influenza and SARS-CoV-2 co-infection at the extremes of age: decipher the ominous tales of immune vulnerability
Advanced Biotechnology, Год журнала: 2025, Номер 3(1)
Опубликована: Янв. 21, 2025
The co-circulation of influenza and SARS-CoV-2 has led to co-infection events, primarily affecting children older adults, who are at higher risk for severe disease. Although prevalence is relatively low, it associated with worse outcomes compared mono-infections. Previous studies have shown that the depend on multiple factors, including viral interference, virus-host interaction host response. Children elderly exhibit distinct patterns antiviral response, which involve airway epithelium, mucociliary clearance, innate adaptive immune cells, inflammatory mediators. This review explores pathogeneses co-infection, focusing responses in elderly. By comparing immature immunity senescence we aim provide insights clinical management cases.
Язык: Английский
Процитировано
1SARS-CoV-2 infects cells lining the blood-retinal barrier and induces a hyperinflammatory immune response in the retina via systemic exposure
PLoS Pathogens, Год журнала: 2024, Номер 20(4), С. e1012156 - e1012156
Опубликована: Апрель 10, 2024
SARS-CoV-2 has been shown to cause wide-ranging ocular abnormalities and vision impairment in COVID-19 patients. However, there is limited understanding of transmission, tropism, associated pathologies. The presence viral RNA corneal/conjunctival tissue tears, along with the evidence entry receptors on surface, led speculation that eye may serve as a potential route transmission. Here, we investigated interaction cells lining blood-retinal barrier (BRB) role its transmission tropism. results from our study suggest exposure does not lung infection moribund illness K18-hACE2 mice despite extended remnants various tissues. In contrast, intranasal only resulted spike (S) protein different tissues but also induces hyperinflammatory immune response retina. Additionally, long-term S-protein caused microaneurysm, retinal pigmented epithelium (RPE) mottling, atrophy, vein occlusion mouse eyes. Notably, BRB, outer barrier, RPE, inner vascular endothelium, were highly permissive replication. Unexpectedly, primary human corneal epithelial comparatively resistant infection. BRB showed induced expression increased susceptibility towards SARS-CoV-2-induced cell death. Furthermore, hyperglycemic conditions enhanced receptor expression, infectivity, death cells, confirming reported heightened pathological manifestations comorbid populations. Collectively, provides first tropism via virus can infect retina systemic permeation induce inflammation.
Язык: Английский
Процитировано
74D-DIA Proteomics Uncovers New Insights into Host Salivary Response Following SARS-CoV-2 Omicron Infection
Journal of Proteome Research, Год журнала: 2025, Номер 24(2), С. 499 - 514
Опубликована: Янв. 13, 2025
Since late 2021, Omicron variants have dominated the epidemiological scenario as most successful severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sublineages, driving new and breakthrough infections globally over past two years. In this study, we investigated for first time host salivary response of COVID-19 patients infected with (BA.1, BA.2, BA.4/5) by using an untargeted four-dimensional data-independent acquisition (4D-DIA)-based proteomics approach. We identified 137 proteins whose abundance levels differed between positive negative groups. Salivary signatures were mainly enriched in ribosomal proteins, linked to mRNAviral translation, protein synthesis processing, immune innate, antiapoptotic signaling. The higher 14-3-3 (YWHAG, YWHAQ, YWHAE, SFN) saliva, reported here, may be associated increased infectivity improved viral replicative fitness. also seven (ACTN1, H2AC2, GSN, NDKA, CD109, GGH, PCYOX) that yielded comprehension into infection performed outstandingly screening a hospital setting. This panel presented enhanced anti-COVID-19 anti-inflammatory signature, providing insights disease severity, supported comparisons other proteome data sets. signature provided valuable host's SARS-CoV-2 infection, shedding light on pathophysiology COVID-19, particularly cases mild disease. It underscores potential clinical applications saliva settings. Data are available via ProteomeXchange identifier PXD054133.
Язык: Английский
Процитировано
0Similar Spatial Expression of Immune‐Related Proteins in SARS‐CoV‐2 Placentitis and Chronic Histiocytic Intervillositis
European Journal of Immunology, Год журнала: 2025, Номер 55(1)
Опубликована: Янв. 1, 2025
ABSTRACT Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection in the placenta can lead to fetal distress and demise, characterized by severe trophoblast necrosis, chronic histiocytic intervillositis (CHI), massive perivillous fibrin deposition. We aimed uncover spatial immune‐related protein changes SARS‐CoV‐2 placentitis compared with CHI placentas uncomplicated pregnancies gain insight into underlying pathophysiological mechanisms. Placentas were retrospectively collected from cases resulting distress/demise ( n = 9), term controls 9). The expression of 53 proteins was quantified using GeoMx Digital Spatial Profiler three separate compartments: villi (fetal compartment), intervillous space, decidua (both maternal compartments). Compared controls, both displayed differentially expressed space only, including upregulation myeloid markers (e.g., CD40, CD11c, CD68, CD163). Specifically, associated reduced multiple apoptotic BAD, BIM, BLXL, BCL6). In conclusion, are enhanced cell infiltration but not villi. more prominently apoptosis‐related may an exaggerated immune response, causing placental dysfunction demise.
Язык: Английский
Процитировано
0The complexities of cell death mechanisms: a new perspective in systemic sclerosis therapy
APOPTOSIS, Год журнала: 2025, Номер unknown
Опубликована: Фев. 9, 2025
Язык: Английский
Процитировано
0Bid Protein: A Participant in the Apoptotic Network with Roles in Viral Infections
International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(6), С. 2385 - 2385
Опубликована: Март 7, 2025
The BH3-interacting domain death agonist (Bid), a proapoptotic signaling molecule of the B-cell lymphoma 2 (Bcl-2) family, is key regulator mitochondrial outer membrane (MOM) permeability. Uniquely positioned at intersection extrinsic and intrinsic apoptosis pathways, Bid links receptor to mitochondria-dependent cascade can also be activated by endoplasmic reticulum (ER) stress. In its active forms, cleaved (cBid) truncated (tBid), it disrupts MOM integrity via Bax/Bak-dependent independent mechanisms. Apoptosis plays dual role in viral infections, either promoting or counteracting propagation. Consequently, viruses modulate favor their replication. deregulation activity contributes oncogenic transformation, inflammation, immunosuppression, neurotoxicity, pathogen propagation during various infections. this work, we explore Bid’s structure, function, activation processes, targeting. We describe induction involvement infections with multiple viruses. Additionally, discuss therapeutic potential antiviral strategies. Understanding pathways offers valuable insights into host–virus interactions pathogenesis This knowledge may facilitate development novel approaches combat virus-associated diseases effectively.
Язык: Английский
Процитировано
0Cyclooxygenase-2/Prostaglandin E2 Pathway Facilitates Infectious Bronchitis Virus-Induced Necroptosis in Chicken Macrophages, a Caspase-Independent Cell Death
Viruses, Год журнала: 2025, Номер 17(4), С. 503 - 503
Опубликована: Март 31, 2025
Infectious bronchitis virus (IBV) poses a major challenge to poultry health and productivity. This study examined how inflammatory cell death pathways influence the replication pathogenesis of two IBV strains—respiratory Connecticut (Conn) A5968 nephropathogenic Delmarva (DMV)/1639—in chicken macrophages. Low serum conditions enhanced viral replication, reduced viability, promoted apoptosis necroptosis, with DMV/1639 showing more pronounced effects. Modulation cyclooxygenase-2/prostaglandin E2 (COX-2/PGE2) pathway displayed strain-specific effects, mitigating necroptosis in DMV/1639-infected cells but exacerbating Conn A5968-infected cells. Broad caspase inhibition (z-VAD-FMK) while selective caspase-1/4 heightened apoptotic responses. Caspase-8 selectively infections increased infections. NLRP3 inflammasome RIPK1 decreased viability both strains had distinct effects on necroptosis. These findings reveal regulation apoptosis, underscoring intricate interplay between host pathways. Understanding these mechanisms provides novel insights into highlights potential therapeutic strategies mitigate its impact health.
Язык: Английский
Процитировано
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