The neurobiology of SARS-CoV-2 infection

Nature reviews. Neuroscience, Journal Year: 2023, Volume and Issue: 25(1), P. 30 - 42

Published: Dec. 4, 2023

Language: Английский

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Direct and indirect impact of SARS-CoV-2 on the brain

Human Genetics, Journal Year: 2023, Volume and Issue: 142(8), P. 1317 - 1326

Published: April 1, 2023

Language: Английский

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Neuroinvasion and neurotropism of severe acute respiratory syndrome coronavirus 2 infection

Current Opinion in Microbiology, Journal Year: 2024, Volume and Issue: 79, P. 102474 - 102474

Published: April 13, 2024

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of disease 2019, contributes to neurological pathologies in nearly 30% patients, extending beyond symptoms. These manifestations encompass disorders both peripheral and central nervous systems, causing among others cerebrovascular issues psychiatric during and/or post-acute infection phases. Despite ongoing research, uncertainties persist about precise mechanism virus uses infiltrate system involved entry portals. This review discusses potential routes, including hematogenous anterograde transport. Furthermore, we explore variations neurotropism, neurovirulence, pandemic-associated variants concern. In conclusion, SARS-CoV-2 can infect numerous cells within system, provoke inflammatory responses, induce neuropathological changes.

Language: Английский

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Virulence Profiles of Wild-Type, P.1 and Delta SARS-CoV-2 Variants in K18-hACE2 Transgenic Mice

Viruses, Journal Year: 2023, Volume and Issue: 15(4), P. 999 - 999

Published: April 19, 2023

Since December 2019, the world has been experiencing COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and we now face emergence of several variants. We aimed to assess differences between wild-type (Wt) (Wuhan) strain P.1 (Gamma) Delta variants using infected K18-hACE2 mice. The clinical manifestations, behavior, virus load, pulmonary capacity, histopathological alterations were analyzed. P.1-infected mice showed weight loss more manifestations than Wt Delta-infected capacity was reduced in compared other groups. Pulmonary histological findings demonstrated that a aggressive disease generated virus. quantification SARS-CoV-2 viral copies varied greatly among although it higher on day death. Our data revealed with variant develop infectious those variants, despite significant heterogeneity

Language: Английский

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The immunobiology of SARS-CoV-2 infection and vaccine responses: potential influences of cross-reactive memory responses and aging on efficacy and off-target effects

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Feb. 26, 2024

Immune responses to both SARS-CoV-2 infection and its associated vaccines have been highly variable within the general population. The increasing evidence of long-lasting symptoms after resolution infection, called post-acute sequelae COVID-19 (PASC) or “Long COVID,” suggests that immune-mediated mechanisms are at play. Closely related endemic common human coronaviruses (hCoV) can induce pre-existing potentially cross-reactive immunity, which then affect primary as well vaccination responses. influence immunity from these hCoVs, generated original CoV2 strains on development new high-affinity antigenic viral variants, needs be better understood given need for continuous vaccine adaptation application in Due part thymic involution, normal aging is with reduced naïve T cell compartments impaired antigen responsiveness, resulting a reliance memory pool may lower affinity, restricted diversity, shorter duration. These effects also mediated by presence down-regulatory anti-idiotype increase aging. Given tremendous heterogeneity clinical data, utilization preclinical models offers greatest ability assess immune under controlled setting. should now involve prior antigen/viral exposure combined incorporation modifying factors such age effects. This will allow mechanistic dissection understanding different pathways involved pathogen potential over time how responses, including efficacy off-target tissues modeling PASC.

Language: Английский

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Upregulation of inflammatory genes and pathways links obesity to severe COVID-19

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Journal Year: 2024, Volume and Issue: 1870(7), P. 167322 - 167322

Published: June 26, 2024

Obesity is a risk factor for developing severe COVID-19. However, the mechanism underlying obesity-accelerated COVID-19 remains unclear. Here, we report results from study in which 2-3-month-old K18-hACE2 (K18) mice were fed western high-fat diet (WD) or normal chow (NC) over 3 months before intranasal infection with sublethal dose of SARS-CoV2 WA1 (a strain ancestral to Wuhan variant). After infection, WD-fed K18 lost significantly more body weight and had lung inflammation than (NC)-fed mice. Bulk RNA-seq analysis lungs adipose tissue revealed diverse landscape various immune cells, inflammatory markers, pathways upregulated infected when compared NC-fed control The transcript levels IL-6, an important marker disease severity, at 6-9 days post-infection Transcriptome obtained deceased patients found that obese increase expression genes activation associated as normal-weight (n = 2). mouse model human patient data support link between phenotype. These also indicate caused by SARS-CoV-2 would be suitable dissecting cellular molecular mechanisms pathogenesis.

Language: Английский

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Tracking inflammation resolution signatures in lungs after SARS-CoV-2 omicron BA.1 infection of K18-hACE2 mice

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 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”.

Language: Английский

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A mouse xenograft long‐term replication yields a SARS‐CoV‐2 Delta mutant with increased lethality

Journal of Medical Virology, Journal Year: 2024, Volume and Issue: 96(2)

Published: Feb. 1, 2024

Abstract We recently established a long‐term SARS‐CoV‐2 infection model using lung‐cancer xenograft mice and identified mutations that arose in the genome during propagation. Here, we applied our to Delta variant, which has increased transmissibility immune escape compared with ancestral SARS‐CoV‐2. observed limited propagation, including two predominant mutations: R682W spike protein L330W nucleocapsid protein. analyzed representative isolates, Delta‐10 Delta‐12, both some additional mutations. Delta‐12 showed lower replication capacity cultured cells; however, was more lethal K18‐hACE2 Delta‐10. Mice infected had higher viral titers, severe histopathology lungs, chemokine expression, astrocyte microglia activation, extensive neutrophil infiltration brain. Brain tissue hemorrhage mild vacuolation were also observed, suggesting high lethality of associated lung brain pathology. Our can provide mutant viruses derived from knowledge about possible contributions emergent properties new variants.

Language: Английский

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Recombinant measles virus expressing prefusion spike protein stabilized by six rather than two prolines is more efficacious against SARS‐CoV‐2 infection

Journal of Medical Virology, Journal Year: 2023, Volume and Issue: 95(4)

Published: March 21, 2023

Measles virus (MeV) has been an excellent vector platform for delivering vaccines against many pathogens because of its high safety and efficacy, induction long-lived immunity. Early in the COVID-19 pandemic, a recombinant MeV (rMeV) expressing prefusion full-length spike protein stabilized by two prolines (TMV-083) was developed tested phase 1 1/2 clinical trials but discontinued insufficient immunogenicity low seroconversion rate adults. Here, we compared rMeV soluble (preS) (rMeV-preS-2P) with preS six (rMeV-preS-6P). We found that rMeV-preS-6P expressed approximately five times more than rMeV-preS-2P cell culture. Importantly, induced 30-60 serum immunoglobulin G neutralizing antibody rMeV-preS-2P, respectively, IFNAR

Language: Английский

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Neuropathological lesions in intravenous BCG-stimulated K18-hACE2 mice challenged with SARS-CoV-2

Veterinary Research, Journal Year: 2024, Volume and Issue: 55(1)

Published: May 31, 2024

Abstract In the wake of COVID-19 pandemic caused by SARS-CoV-2, questions emerged about potential effects Bacillus Calmette-Guérin (BCG) vaccine on immune response to SARS-CoV-2 infection, including neurodegenerative diseases it may contribute to. To explore this, an experimental study was carried out in BCG-stimulated and non-stimulated k18-hACE2 mice challenged with SARS-CoV-2. Viral loads tissues determined RT-qPCR, histopathology brain lungs, immunohistochemical (IHC) as well mortality rates, clinical signs plasma inflammatory coagulation biomarkers were assessed. Our results showed BCG-SARS-CoV-2 presented higher viral increased frequency neuroinvasion, greatest differences observed between groups at 3–4 days post-infection (dpi). Histopathological examination a severity lesions mice, mainly consisting neuroinflammation, glial cell population neuronal degeneration, from 5 dpi onwards. This group also interstitial pneumonia vascular thrombosis lungs (3–4 dpi), values for TNF-α D-dimer values, while iNOS dpi. Results this indicate that BCG stimulation could have intensified promoting virus neuroinvasion dissemination model. Although show hACE2 expression neurodissemination, suggests that, although benefits enhancing heterologous protection against pathogens tumour cells been broadly demonstrated, adverse outcomes due non-specific should be considered.

Language: Английский

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