SARS-CoV-2 ORF8 as a Modulator of Cytokine Induction: Evidence and Search for Molecular Mechanisms

Viruses, Год журнала: 2024, Номер 16(1), С. 161 - 161

Опубликована: Янв. 22, 2024

Severe cases of SARS-CoV-2 infection are characterized by an immune response that leads to the overproduction pro-inflammatory cytokines, resulting in lung damage, cardiovascular symptoms, hematologic acute kidney injury and multiple organ failure can lead death. This remarkable increase cytokines other inflammatory molecules is primarily caused viral proteins, particular interest has been given ORF8, a unique accessory protein specific SARS-CoV-2. Despite plenty research, precise mechanisms which ORF8 induces proinflammatory not clear. Our investigations demonstrated augments production IL-6 induced Poly(I:C) human embryonic (HEK)-293 monocyte-derived dendritic cells (mono-DCs). We discuss our findings multifaceted roles as modulator cytokine response, focusing on type I interferon IL-6, key component In addition, we explore hypothesis may act through pattern recognition receptors dsRNA such TLRs.

Язык: Английский

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Host factors of SARS-CoV-2 in infection, pathogenesis, and long-term effects

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

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Regulation of virion production by the ORF8 signal peptide across SARS-CoV-2 variants

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Март 6, 2024

The open reading frame 8 (ORF8), an accessory protein of SARS-CoV-2, is prone to deletions and mutations across different viral variants, which was first described in several Singapore variants. reason why evolution favors loss or inactivation ORF8 not fully understood, although the effects on inflammation, immune evasion, disease severity have been described. Here we show using clinical deficient isolates, virus like particles (VLPs) replicons that expression dampens particle production. physically interacts with Spike induces Golgi fragmentation, overall contributing less Using systematic deletions, mapped reducing function its N terminal signal peptide. Interestingly, this part severely truncated recent XBB.1.5 variant, when restored, suppresses production context entire genome. Collectively, our data support model evolutionary pressure exists delete sequence SARS-CoV-2 variants enable

Язык: Английский

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SARS-CoV-2 Impairs Osteoblast Differentiation Through Spike Glycoprotein and Cytokine Dysregulation

Viruses, Год журнала: 2025, Номер 17(2), С. 143 - 143

Опубликована: Янв. 22, 2025

Pulmonary and extrapulmonary manifestations have been reported following infection with SARS-CoV-2, the causative agent of COVID-19. The virus persists in multiple organs due to its tropism for various tissues, including skeletal system. This study investigates effects SARS-CoV-2 infection, both ancestral Omicron viral strains, on differentiating mesenchymal stem cells (MSCs), precursor cells, into osteoblasts. Although strains can productively infect osteoblasts, cell remained abortive. Viral exposure during osteoblast differentiation demonstrates that variants inhibit mineral organic matrix deposition. is accompanied by reduced expression runt-related transcription factor 2 (RUNX2) increased levels interleukin-6 (IL-6), a cytokine negatively regulates differentiation. Furthermore, upregulation receptor activator nuclear kappa B ligand (RANKL) strongly suggests may disrupt bone homeostasis promoting osteoclast differentiation, ultimately leading formation bone-resorbing cells. process dependent spike glycoprotein since neutralization significantly effect infective UV-C inactivated virus. underscores capacity essential preserving functionality tissue.

Язык: Английский

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Beyond Infection: The Role of Secreted Viral Proteins in Pathogenesis, Disease Severity and Diagnostic Applications

Cells, Год журнала: 2025, Номер 14(9), С. 624 - 624

Опубликована: Апрель 22, 2025

Secreted viral proteins are crucial in virus–host interactions, as they modify the host microenvironment to promote infection. These secreted could alter immune and inflammatory responses, allowing viruses evade defense mechanisms such cytotoxic T cell activation antibody neutralization. Some mimic molecules suppress antiviral making them valuable targets for antivirals diagnostics. Notable examples include BARF1 from Epstein–Barr virus, associated with gastric cancer; vIL-10 which regulates responses contributes autoimmune diseases; NS1 dengue vascular permeability early diagnosis; NSP4 rotavirus an enterotoxin, among others. The study of these improves our understanding pathogenesis helps develop innovative treatments infectious non-infectious diseases, taking advantage evolutionary adaptations viruses. This review explores their impact on infection cycle, disease progression, key processes, cycle regulation, apoptosis, signaling. Research deepens basic knowledge virology generates alternative methods detecting biomarkers creating more effective therapies, well implementing some emerging technologies, biosensors plasmon resonance, diagnosis diseases.

Язык: Английский

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SARS-CoV-2 Modulation of HIV Latency Reversal in a Myeloid Cell Line: Direct and Bystander Effects

Viruses, Год журнала: 2024, Номер 16(8), С. 1310 - 1310

Опубликована: Авг. 17, 2024

Coronavirus disease 2019 (COVID-19) might impact progression in people living with HIV (PLWH), including those on effective combination antiretroviral therapy (cART). These individuals often experience chronic conditions characterized by proviral latency or low-level viral replication CD4+ memory T cells and tissue macrophages. Pro-inflammatory cytokines, such as TNF-α, IL-1β, IL-6, IFN-γ, can reactivate provirus expression both primary cell lines. cytokines are elevated infected SARS-CoV-2, the virus causing COVID-19. However, it is still unknown whether SARS-CoV-2 modulate reactivation cells. Here, we report that exposure of chronically HIV-1-infected myeloid line U1 to two different isolates (ancestral BA.5) reversed its latent state after 24 h. We also observed human monocyte-derived macrophages (MDM) initially drove their polarization towards an M1 phenotype, which shifted M2 over time. This effect was associated soluble factors released during initial phase reactivated production cells, like MDM stimulated TLR agonist resiquimod. Our study suggests SARS-CoV-2-induced systemic inflammation interaction could influence HIV-1 PLWH.

Язык: Английский

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Insights into COVID-19: Perspectives on Drug Remedies and Host Cell Responses

Biomolecules, Год журнала: 2023, Номер 13(10), С. 1452 - 1452

Опубликована: Сен. 26, 2023

In light of the COVID-19 global pandemic caused by SARS-CoV-2, ongoing research has centered on minimizing viral spread either stopping entry or inhibiting replication. Repurposing antiviral drugs, typically nucleoside analogs, proven successful at virus This review summarizes current information regarding coronavirus classification and characterization presents broad clinical consequences SARS-CoV-2 activation angiotensin-converting enzyme 2 (ACE2) receptor expressed in different human cell types. It provides publicly available knowledge chemical nature proposed therapeutics their target biomolecules to assist identification potentially new drugs for treatment infection.

Язык: Английский

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SARS‐COV‐2 ORF8 as a Modulator of Cytokine Induction: Evidence and Search for Molecular Mechanisms

Опубликована: Ноя. 30, 2023

Severe cases of SARS-CoV-2 infection are characterized by an immune response that leads to the overproduction pro-inflammatory cytokines, resulting in damage lungs and other organs. This remarkable increase cytokines inflammatory molecules is primary caused viral proteins, particular ORF8, a unique accessory protein specific SARS-CoV-2. In addition its role cytokine induction, ORF8 attributed with various functions, including ability evade type I interferon responses. Despite evidence, mechanisms through which exerts these functions remains subject controversy. this mini review, we discuss multifaceted roles as modulator response, focusing on IL-6. We also data from our studies indicating augments production IL-6 induced Poly(I:C) human embryonic kidney (HEK)-293 monocyte-derived dendritic cells (mono-DCs).

Язык: Английский

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An enhanced IL17 and muted type I interferon nasal epithelial cell state characterizes severe COVID-19 with fungal coinfection

Microbiology Spectrum, Год журнала: 2024, Номер 12(6)

Опубликована: Апрель 30, 2024

Recent case reports and epidemiological data suggest that fungal infections represent an underappreciated complication among people with severe COVID-19. However, the frequency of colonization in patients COVID-19 associations specific immune responses airways remain incompletely defined. We previously generated a single-cell RNA-sequencing set characterizing upper respiratory microenvironment during mapped relationship between disease severity local behavior nasal epithelial cells infiltrating cells. Our previous study, agreement findings from related human cohorts, demonstrated profound deficiency host immunity, particularly type I III interferon signaling tract, is associated rapid progression to worse clinical outcomes. have now performed further analysis this cohort identified subset participants concurrent detection Candida species-derived transcripts within samples collected nasopharynx trachea. Here, we present characteristics these individuals. Using matched transcriptomic profiles individuals' mucosa, identify signatures suggestive IL17 stimulation anti-fungal immunity. Further, observe significant expression inflammatory cascades tracheal epithelium all who went on develop COVID-19, even without detectable genetic material pathogens. Together, our stimulation-in part driven by colonization-and blunted common feature infection. In paper, suggesting symptomatic asymptomatic coinfections can impact patient hospitalization. By looking into presence other pathogens their effect response hospitalizations, aim offer insight underestimated scenario, furthering current knowledge determinants could be considered for future diagnostic intervention strategies.

Язык: Английский

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Hidden evolutionary constraints dictate the retention of coronavirus accessory genes

Current Biology, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 1, 2024

Язык: Английский

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