Neuroinvasion and Neurotropism by SARS-CoV-2 Variants in the K18-hACE2 Mouse

Viruses, Год журнала: 2022, Номер 14(5), С. 1020 - 1020

Опубликована: Май 11, 2022

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) not only affects the respiratory tract but also causes neurological symptoms such as loss of smell and taste, headache, fatigue or severe cerebrovascular complications. Using transgenic mice expressing human angiotensin-converting enzyme (hACE2), we investigated spatiotemporal distribution pathomorphological features in CNS following intranasal infection with SARS-CoV-2 variants, well after prior influenza A virus infection. Apart from Omicron, found all variants to frequently spread within CNS. Infection was restricted neurons appeared olfactory bulb mainly basally oriented regions brain into spinal cord, independent ACE2 expression without evidence neuronal cell death, axonal damage demyelination. However, microglial activation, microgliosis a mild macrophage T dominated inflammatory response consistently observed, accompanied by apoptotic death endothelial, immune cells, their apparent Microgliosis apoptosis indicate potential role microglia for pathogenesis viral effect COVID-19 possible impairment functions, especially long COVID. These data may be informative selection therapeutic candidates broadly support investigation agents adequate penetration relevant

Язык: Английский

---

The Pathophysiology of Long COVID throughout the Renin-Angiotensin System

Molecules, Год журнала: 2022, Номер 27(9), С. 2903 - 2903

Опубликована: Май 2, 2022

COVID-19 has expanded across the world since its discovery in Wuhan (China) and had a significant impact on people's lives health. Long COVID is term coined by World Health Organization (WHO) to describe variety of persistent symptoms after acute SARS-CoV-2 infection. been demonstrated affect various SARS-CoV-2-infected persons, independently disease severity. The long COVID, like COVID-19, consist set damage organs systems such as respiratory, cardiovascular, neurological, endocrine, urinary, immune systems. Fatigue, dyspnea, cardiac abnormalities, cognitive attention impairments, sleep disturbances, post-traumatic stress disorder, muscle pain, concentration problems, headache were all reported COVID. At molecular level, renin-angiotensin system (RAS) heavily involved pathogenesis this illness, much it phase viral In review, we summarize several tissues, with special focus significance RAS pathogenesis. risk factors potential therapy approaches are also explored.

Язык: Английский

---

ZBP1: A Powerful Innate Immune Sensor and Double-Edged Sword in Host Immunity

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(18), С. 10224 - 10224

Опубликована: Сен. 6, 2022

Z-conformation nucleic acid binding protein 1 (ZBP1), a powerful innate immune sensor, has been identified as the important signaling initiation factor in response and multiple inflammatory cell death known PANoptosis. The of ZBP1 requires recognition left-handed double-helix Z-nucleic (includes Z-DNA Z-RNA) subsequent transduction depends on interaction between its adapter proteins, such TANK-binding kinase (TBK1), interferon regulatory 3 (IRF3), receptor-interacting serine/threonine-protein (RIPK1), RIPK3. activated immunity, including type-I (IFN-I) NF-κB signaling, constitutes an line defense against pathogenic infection. In addition, ZBP1-mediated PANoptosis is double-edged sword anti-infection, auto-inflammatory diseases, tumor immunity. beneficial for eliminating infected cells cells, but abnormal or excessive can lead to strong that harmful host. Thus, pathogens host have each developed multiplex tactics targeting maintain virulence homeostasis. this paper, we reviewed mechanisms effects immunity pathogen infection, various antagonistic strategies ZBP1. We also discuss existent gaps regarding forecast potential directions future research.

Язык: Английский

---

Choosing a cellular model to study SARS-CoV-2

Frontiers in Cellular and Infection Microbiology, Год журнала: 2022, Номер 12

Опубликована: Окт. 21, 2022

As new pathogens emerge, challenges must be faced. This is no different in infectious disease research, where identifying the best tools available laboratories to conduct an investigation can, at least initially, particularly complicated. However, context of emerging virus, such as SARS-CoV-2, which was recently detected China and has become a global threat healthcare systems, developing models infection pathogenesis urgently required. Cell-based approaches are crucial understanding coronavirus biology, growth kinetics, tropism. Usually, laboratory cell lines first line experimental study viral pathogenicity perform assays aimed screening antiviral compounds efficient blocking replication viruses, saving time resources, reducing use animals. determining ideal type can challenging, especially when several researchers have adapt their studies specific requirements. review strives guide scientists who venturing into studying SARS-CoV-2 help them choose right cellular models. It revisits basic concepts virology presents currently

Язык: Английский

---

The role of cell death in SARS-CoV-2 infection

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Сен. 20, 2023

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), showing high infectiousness, resulted in an ongoing pandemic termed disease 2019 (COVID-19). COVID-19 cases often experience distress syndrome, which has caused millions of deaths. Apart from triggering inflammatory and immune responses, many viral infections can cause programmed cell death infected cells. Cell mechanisms have a vital role maintaining suitable environment to achieve normal functionality. Nonetheless, these processes are dysregulated, potentially contributing pathogenesis. Over the past decades, multiple pathways becoming better understood. Growing evidence suggests that induction by may significantly contributes infection pathogenicity. However, interaction SARS-CoV-2 with death, together its associated mechanisms, is yet be elucidated. In this review, we summarize existing concerning molecular modulation as well viral-host interactions, shed new light on antiviral therapy against SARS-CoV-2.

Язык: Английский

---

Full protection from SARS-CoV-2 brain infection and damage in susceptible transgenic mice conferred by MVA-CoV2-S vaccine candidate

Nature Neuroscience, Год журнала: 2023, Номер 26(2), С. 226 - 238

Опубликована: Янв. 9, 2023

Язык: Английский

---

SARS-CoV-2 omicron BA.5 and XBB variants have increased neurotropic potential over BA.1 in K18-hACE2 mice and human brain organoids

Frontiers in Microbiology, Год журнала: 2023, Номер 14

Опубликована: Ноя. 23, 2023

The reduced pathogenicity of the omicron BA.1 sub-lineage compared to earlier variants is well described, although whether such attenuation retained for later like BA.5 and XBB remains controversial. We show that isolates were significantly more pathogenic in K18-hACE2 mice than a isolate, showing increased neurotropic potential, resulting fulminant brain infection mortality, similar seen original ancestral isolates. also infected human cortical organoids greater extent In brains mice, neurons main target infection, neuronal progenitor cells immature infected. results herein suggest evolving may have increasing potential.

Язык: Английский

---

Z-DNA binding protein 1 orchestrates innate immunity and inflammatory cell death

Cytokine & Growth Factor Reviews, Год журнала: 2024, Номер 77, С. 15 - 29

Опубликована: Март 26, 2024

Язык: Английский

---

ZBP1-Mediated Necroptosis: Mechanisms and Therapeutic Implications

Molecules, Год журнала: 2022, Номер 28(1), С. 52 - 52

Опубликована: Дек. 21, 2022

Cell death is a fundamental pathophysiological process in human disease. The discovery of necroptosis, form regulated necrosis that induced by the activation receptors and formation necrosome, represents major breakthrough field cell past decade. Z-DNA-binding protein (ZBP1) an interferon (IFN)-inducing protein, initially reported as double-stranded DNA (dsDNA) sensor, which induces innate inflammatory response. Recently, ZBP1 was identified important sensor necroptosis during virus infection. It connects viral nucleic acid receptor-interacting kinase 3 (RIPK3) via two domains necrosome. Recent studies have also non-viral infections mediates necrotic signal transduction unique mechanism. This review highlights its novel findings provides insight into critical role crosstalk between different types death, may represent new therapeutic option.

Язык: Английский

---

Recent advances in ZBP1-derived PANoptosis against viral infections

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Май 16, 2023

Innate immunity is an important first line of defense against pathogens, including viruses. These pathogen- and damage-associated molecular patterns (PAMPs DAMPs, respectively), resulting in the induction inflammatory cell death, are detected by specific innate immune sensors. Recently, Z-DNA binding protein 1 (ZBP1), also called DNA-dependent activator IFN regulatory factor (DAI) or DLM1, reported to regulate death as a central mediator during viral infection. ZBP1 interferon (IFN)-inducible gene that contains two Z-form nucleic acid-binding domains (Zα1 Zα2) N-terminus receptor-interacting homotypic interaction motifs (RHIM1 RHIM2) middle, which interact with other proteins RHIM domain. By sensing entry RNA, induces PANoptosis, protects host cells infections, such influenza A virus (IAV) herpes simplex (HSV1). However, some viruses, particularly coronaviruses (CoVs), induce PANoptosis hyperactivate system, leading cytokine storm, organ failure, tissue damage, even death. In this review, we discuss mechanism ZBP1-derived pro-inflammatory cytokines influence double-edged sword results cell. Understanding may be critical for improving therapeutic strategies.

Язык: Английский

---