Опубликована: Янв. 1, 2024
Язык: Английский
The FASEB Journal, Год журнала: 2025, Номер 39(4)
Опубликована: Фев. 14, 2025
Abstract COVID‐19 commonly leads to respiratory issues, yet numerous patients also exhibit a diverse range of neurological conditions, suggesting detrimental impact SARS‐CoV‐2 or the viral Spike protein on central nervous system. Nonetheless, molecular pathway behind pathology and presumed neurotropism remains largely unexplored. We generated human cortical organoids (HCOs) derived from induced pluripotent stem cells (hiPSC) assess: (1) expression main entry factors; (2) their vulnerability infection; (3) infection exposure transcriptome. Results proved that HCOs express receptors co‐receptors; may be productively infected by SARS‐CoV‐2; particles released SARS‐CoV‐2‐infected are able re‐infect another cellular line; (4) resulted in activation apoptotic stress pathways, along with inflammatory processes. Notably, these effects were recapitulated when exposed alone. The data obtained demonstrate likely infects probably through binding ACE2, CD147, NRP1 factors. Furthermore, alone sufficient disrupt homeostasis induce neurotoxic effects, potentially contributing onset long‐COVID symptoms.
Язык: Английский
Процитировано
2
Frontiers in Immunology, Год журнала: 2024, Номер 15
Опубликована: Май 13, 2024
Introduction Global microplastic (MP) pollution is now well recognized, with humans and animals consuming inhaling MPs on a daily basis, growing body of concern surrounding the potential impacts human health. Methods Using mouse model mild COVID-19, we describe herein effects azide-free 1 μm polystyrene MP beads, co-delivered into lungs SARS-CoV-2 omicron BA.5 inoculum. The effect host response to infection was analysed using histopathology RNA-Seq at 2 6 days post-infection (dpi). Results Although reduced clearance from lung, virus titres viral RNA levels were not significantly affected by MPs, overt MP-associated clinical or histopathological changes observed. However, infected revealed that exposure suppressed innate immune responses dpi increased pro-inflammatory signatures dpi. cytokine profile showed significant correlation ‘cytokine release syndrome’ signature observed in some COVID-19 patients. Discussion findings are consistent recent finding can inhibit phagocytosis apoptotic cells via binding Tim4. They also add literature suggesting dysregulate inflammatory processes specific disease settings.
Язык: Английский
Процитировано
10
Cell Reports, Год журнала: 2024, Номер 43(11), С. 114921 - 114921
Опубликована: Ноя. 1, 2024
Angiotensin-converting enzyme 2 (ACE2) is the primary entry receptor for severe acute respiratory syndrome coronavirus (SARS-CoV-2), but ACE2-independent has been observed in vitro strains with spike-E484D substitution. Here, we conduct a whole-genome CRISPR-Cas9 knockout screen using SARS-CoV-2 mouse adapted 1 (SARS-CoV-2
Язык: Английский
Процитировано
5
Biomedicines, Год журнала: 2025, Номер 13(1), С. 246 - 246
Опубликована: Янв. 20, 2025
The escalating issue of air pollution contributes to an alarming number premature fatalities each year, thereby posing a significant threat global health. focus recent research has shifted towards understanding its potential association with neurodegenerative diseases, specifically Alzheimer’s disease (AD). AD is recognised for characteristic deposition toxic proteins within the brain, leading steady deterioration cognitive capabilities, memory failure, and, ultimately, death. There burgeoning evidence implying that may be contributing factor this protein build up, intensifying course AD. It been demonstrated olfactory system, responsible smell perception and processing, acts as gateway airborne pollutants inflict brain damage. This review aims elucidate relationship between pollution, deterioration, Additionally, highlight mechanisms through which might instigate development role system in pathogenesis. Moreover, diverse model systems employed exploring correlation, public health policy ramifications, prospective directions future will discussed.
Язык: Английский
Процитировано
0
Viruses, Год журнала: 2025, Номер 17(4), С. 500 - 500
Опубликована: Март 30, 2025
The global impact of the COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), persists in part due to emergence new variants. Understanding variant-specific infection dynamics and pathogenesis murine models is crucial for identifying phenotypic changes guiding development countermeasures. To address limitations earlier studies that investigated only a few variants or used small sample sizes, we evaluated clinical disease, kinetics, viral titers, cellular localization, histopathologic lungs brains transgenic B6.Cg-Tg(K18-ACE2)2Prlmn/J (“K18”) corresponding genetic control (C57BL/6J) mice expressing human angiotensin-converting enzyme (hACE2). Six SARS-CoV-2 were assessed: B.1 (WA1-like), alpha, beta, delta, omicron, omicron XBB.1.5, using cohorts ≥18 mice. Following intranasal inoculation with B.1, delta variants, K18 experienced rapid weight loss reached euthanasia criteria 5–6 days post-inoculation (dpi). In contrast, inoculated both recovered their starting within 4–6 dpi. Infectious was detected oropharynx at 1 and2 dpi, 2, 4, 6 brain 4 dpi all except omicron. nucleoprotein detected, interstitial pneumonia varying severity observed infected Brain lesions identified As express hACE2 brain—a feature not present humans—we also compared three those mouse-adapted WA1 strain C57BL/6J lacking ACE2 gene. did experience lethal exhibited milder pneumonia, had no evidence neuroinvasion despite similar kinetics These findings demonstrate contrasting phenotypes across two reduced tropism pathology models. This comprehensive analysis mouse provides valuable insights model variant selection future studies.
Язык: Английский
Процитировано
0
Journal of Infection, Год журнала: 2025, Номер unknown, С. 106489 - 106489
Опубликована: Апрель 1, 2025
Язык: Английский
Процитировано
0
bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown
Опубликована: Март 13, 2024
Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes Coronavirus Disease 2019 (COVID-19), which can result in disease, often characterised by a ‘cytokine storm’ and the associated distress syndrome. However, many infections with SARS-CoV-2 are mild or asymptomatic throughout course of infection. Although blood biomarkers disease well studied, less understood inflammatory signatures lung tissues silent infections, wherein infection inflammation rapidly resolved leading to sequelae-free recovery. Herein we described RNA-Seq histological analyses lungs over time an omicron BA.1/K18-hACE2 mouse model, displays these latter features. robust was evident at days post (dpi), viral RNA largely cleared 10 dpi. Acute showed slightly different pattern cytokine compared models, where much diminished 30 dpi absent 66 Cellular deconvolution identified significantly increased abundance scores for number anti-inflammatory pro-resolution cell types 5/10 These included type II innate lymphoid cells, T regulatory interstitial macrophages. Genes whose expression trended downwards – were pathways. upward during this period recovery ciliated AT2 AT1 transition, reticular fibroblasts indicating return homeostasis. Very few differentially expressed host genes dpi, suggesting near complete parallels between subclinical humans those observed model discussed reference concept “protective inflammation”.
Язык: Английский
Процитировано
3
Reviews in Medical Virology, Год журнала: 2024, Номер 34(6)
Опубликована: Ноя. 1, 2024
Abstract The emergence of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) in December 2019 triggered a swift global spread, leading to devastating pandemic. Alarmingly, approximately one four individuals diagnosed with disease (COVID‐19) experience varying degrees cognitive impairment, raising concerns about potential increase neurological sequelae cases. Neuroinflammation seems be the key pathophysiological hallmark linking mild COVID‐19 fatigue, and patients, highlighting interaction between nervous immune systems following SARS‐CoV‐2 infection. Several hypotheses have been proposed explain how virus disrupts physiological pathways trigger inflammation within CNS, potentially neuronal damage. These include neuroinvasion, systemic inflammation, disruption lung gut‐brain axes, reactivation latent viruses. This review explores origins neuroinflammation underlying neuroimmune cross‐talk, important unanswered questions field. Addressing these fundamental issues could enhance our understanding virus's impact on CNS inform strategies mitigate its detrimental effects.
Язык: Английский
Процитировано
3
bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown
Опубликована: Май 8, 2024
ABSTRACT Angiotensin converting enzyme 2 (ACE2) serves as the primary entry receptor for severe acute respiratory syndrome coronavirus (SARS-CoV-2). However, ACE2-independent has been observed in vitro SARS-CoV-2 strains containing E484D amino acid substitution spike protein. In this study, we conducted a whole genome CRISPR-Cas9 knockout screen using strain spike-E484D (SARS-CoV-2 MA1 ) to identify mechanisms. Our findings revealed that infection HEK293T cells relied on heparan sulfate and endocytic pathways, with TMEM106B emerging most significant contributor. While productively infected human brain organoids K18-hACE2 mouse brains, it did not infect C57BL/6J or Ifnar -/- brains. This suggests via TMEM106B, which is protein predominantly expressed brain, overtly increase risk of neuroinvasiveness wild-type mice. Importantly, replicate Ace2 tracts. Overall, robust by likely phenomenon specific conditions, no apparent clinical implications.
Язык: Английский
Процитировано
1
Frontiers in Microbiology, Год журнала: 2024, Номер 15
Опубликована: Сен. 4, 2024
The severity of Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is often dictated a range comorbidities. A considerable literature suggests iron deficiency and overload may contribute to increased infection, inflammation severity, although direct causal relationships have been difficult establish.
Язык: Английский
Процитировано
1