Pedagogical insights from immune responses: analyzing Covid-19's severity through systemic immune-inflammation indexes and gene expressions DOI Creative Commons

Nívia Nonato Silva,

Fabiane da Silva Reis-Goes,

Taiane de Macêdo Gondim

и другие.

Caderno Pedagógico, Год журнала: 2023, Номер 20(4), С. 691 - 716

Опубликована: Ноя. 17, 2023

Following the COVID-19 pandemic, it's crucial to understand relationship between immune responses and clinical results, which also underpins interdisciplinary educational discussions. This study goes beyond standard medical evaluation, linking medicine sociodemography, genetics, education, emphasizing importance of an interconnected view for a comprehensive understanding. Severe cases show imbalances in system, highlighting need early precise prognosis, given its wider sociodemographic consequences. aims investigate potential associations systemic immune-inflammation indexes, gene expression IFNA1, IFN receptors, IL17A, plasmatic IFN-gamma patients. Our observational recruited 67 patients, both mild (28) or severe (39). Data was gathered on demographics, symptoms, laboratory results. Blood tests were used analyze expressions plasma IFNG levels. Most males (61.5%) black ethnic group (87.2%), with clear age difference compared cases. Elevated levels measures seen cases, IFNA1 IL17A increasing, whereas IFNAR1 more common From pedagogical standpoint, emphasizes link findings, genetics data, underlining profound implications education. It suggests using specific hematological as severity indicators underscores further research validate explore broader implications.

Язык: Английский

Initiator cell death event induced by SARS-CoV-2 in the human airway epithelium DOI Open Access
Kaixin Liang, Katherine C. Barnett, Martin Hsu

и другие.

Science Immunology, Год журнала: 2024, Номер 9(97)

Опубликована: Июль 12, 2024

Virus-induced cell death is a key contributor to COVID-19 pathology. Cell induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) well studied in myeloid cells but less its primary host type, angiotensin-converting enzyme (ACE2)–expressing human airway epithelia (HAE). SARS-CoV-2 induces apoptosis, necroptosis, and pyroptosis HAE organotypic cultures. Single-cell limiting-dilution analysis revealed that necroptosis the event infected cells, whereas uninfected bystanders undergo occurs later during infection. Mechanistically, viral Z-RNA binding Z-DNA–binding protein 1 (ZBP1) lung tissues from patients with COVID-19. The Delta (B.1.617.2) variant, which causes more disease than Omicron (B1.1.529) humans, associated orders of magnitude–greater Z-RNA/ZBP1 interactions, severity animal models. Thus, robust ZBP1-mediated severity.

Язык: Английский

Процитировано

11
The antiviral state of the cell: lessons from SARS-CoV-2 DOI
Jérémie Le Pen, Charles M. Rice

Current Opinion in Immunology, Год журнала: 2024, Номер 87, С. 102426 - 102426

Опубликована: Апрель 1, 2024

Язык: Английский

Процитировано

7
A genome-wide arrayed CRISPR screen identifies PLSCR1 as an intrinsic barrier to SARS-CoV-2 entry that recent virus variants have evolved to resist DOI Creative Commons
Jérémie Le Pen,

Gabrielle Paniccia,

Volker Kinast

и другие.

PLoS Biology, Год журнала: 2024, Номер 22(9), С. e3002767 - e3002767

Опубликована: Сен. 24, 2024

Interferons (IFNs) play a crucial role in the regulation and evolution of host–virus interactions. Here, we conducted genome-wide arrayed CRISPR knockout screen presence absence IFN to identify human genes that influence Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. We then performed an integrated analysis interacting with SARS-CoV-2, drawing from selection 67 large-scale studies, including our own. identified 28 high relevance both genetic studies Disease 2019 (COVID-19) patients functional screens cell culture, many related pathway. Among these was IFN-stimulated gene PLSCR1 . did not require induction restrict SARS-CoV-2 contribute signaling. Instead, specifically restricted spike-mediated entry. The PLSCR1-mediated restriction alleviated by TMPRSS2 overexpression, suggesting primarily restricts endocytic entry route. In addition, recent variants have adapted circumvent barrier via currently undetermined mechanisms. Finally, investigate effects present humans discuss association between severe COVID-19 reported recently.

Язык: Английский

Процитировано

6
Cellular RNA interacts with MAVS to promote antiviral signaling DOI
Nandan S. Gokhale, Russell K. Sam, Kim Somfleth

и другие.

Science, Год журнала: 2024, Номер 386(6728)

Опубликована: Дек. 19, 2024

Antiviral signaling downstream of RIG-I–like receptors (RLRs) proceeds through a multi-protein complex organized around the adaptor protein mitochondrial antiviral (MAVS). Protein function can be modulated by RNA molecules that provide allosteric regulation or act as molecular guides scaffolds. We hypothesized plays role in organizing MAVS platforms. found MAVS, its central intrinsically disordered domain, directly interacted with 3′ untranslated regions cellular messenger RNAs. Elimination ribonuclease treatment disrupted signalosome, including RNA-modulated interactors regulate RLR and viral restriction, inhibited phosphorylation transcription factors induce interferons. This work uncovered for promoting highlights generalizable principles regulatory control immune complexes.

Язык: Английский

Процитировано

4
Modeling suggests SARS-CoV-2 rebound after nirmatrelvir-ritonavir treatment is driven by target cell preservation coupled with incomplete viral clearance DOI Creative Commons
Tin Phan, Ruy M. Ribeiro,

Gregory E. Edelstein

и другие.

Journal of Virology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 4, 2025

ABSTRACT In a subset of SARS-CoV-2-infected individuals treated with the antiviral nirmatrelvir-ritonavir, virus rebounds following treatment. The mechanisms driving this rebound are not well understood. We used mathematical model to describe longitudinal viral load dynamics 51 20 whom rebounded. Target cell preservation, either by robust innate immune response or initiation N-R near time symptom onset, coupled incomplete clearance, appears be main factor leading rebound. Moreover, occurrence is likely influenced treatment relative progression infection, earlier treatments higher chance A comparison an untreated cohort suggests that early nirmatrelvir-ritonavir may associated delay in onset adaptive response. Nevertheless, our demonstrates extending course 10-day regimen greatly diminish people mild-to-moderate COVID-19 and who at high risk severe disease. Altogether, results suggest some individuals, standard 5-day starting around completely eliminate virus. Thus, after ends, can if effective has fully developed. These findings on role target preservation clearance also offer possible explanation for other SARS-CoV-2. IMPORTANCE Nirmatrelvir-ritonavir initial reduction followed once stopped. show timing influence stops growth preserves cells but lead full adequately developed, remaining Our provide insights into help develop better strategies minimize possibility.

Язык: Английский

Процитировано

0
Single-cell transcriptomics reveals a compartmentalized antiviral interferon response in the nasal epithelium of mice DOI Creative Commons
Xuefei Wang, Meng Dong,

Xinchao Wu

и другие.

Journal of Virology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 4, 2025

ABSTRACT Type III interferons (IFNs) primarily act on epithelial cells and protect against virus infection of the mucosa, whereas type I IFNs more systemically. To date, it has been unknown which subtypes in upper airways, primary site for initial most respiratory viruses, rely IFN or antiviral protection. address this question, we performed a single-cell transcriptomics analysis IFN-mediated response focusing airways mice. This work identified nine distinct cell types derived from olfactory epithelium thirteen epithelium. Interestingly, induced stronger transcriptional than cells, including sustentacular (SUS) Bowman’s gland (BGC), was dominant compared to IFN. SUS BGC, provide structural support maintain integrity sensory neurons, were highly susceptible with mouse-adapted variant severe acute syndrome coronavirus 2 (SARS-CoV-2 MA20) but protected if animals prophylactically treated These findings demonstrate high degree heterogeneity terms interferon-mediated responses reveal potent role protecting IMPORTANCE SARS-CoV-2 infects BGC epithelium, causing an impairment neurons that can result dysfunctions. We observed unexpected compartmentalization within airway found preferentially respond IFN, resulted robust protection BGC. Given proximity central nervous system, hypothesize evolution favored IFN-biased immune tissue limit inflammatory brain. Cell type-specific triggered by different IFNs, should be investigated detail carefully taken into consideration during development IFN-based antivirals clinical use.

Язык: Английский

Процитировано

0
IFIT3: a crucial mediator in innate immunity and tumor progression with therapeutic implications DOI Creative Commons
Rihan Wu, Hao Yang, Chunlei Liu

и другие.

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Фев. 24, 2025

Interferon-Induced Protein with Tetratricopeptide Repeats 3 (IFIT3) plays a dual role in innate immunity and tumor immunity, functioning as both viral defense molecule regulator of progression. This review explores the mechanisms through which IFIT3 modulates immune responses, including interferon signaling, RIG-I-like receptors, NF-κB pathway. facilitates evasion promotes inflammation-mediated growth by regulating checkpoints microenvironment, its emerging target for cancer immunotherapy opens new avenues therapeutic strategies. Finally, this paper underscores IFIT3's potential clinical applications modulation highlighting need further research on IFIT3-targeted therapies.

Язык: Английский

Процитировано

0
Interferon-stimulated genes and their antiviral activity against SARS-CoV-2 DOI Creative Commons
Ana María Ortega-Prieto, Jose M. Jiménez-Guardeño

mBio, Год журнала: 2024, Номер 15(9)

Опубликована: Авг. 22, 2024

ABSTRACT The coronavirus disease 2019 (COVID-19) pandemic remains an international health problem caused by the recent emergence of severe acute respiratory syndrome 2 (SARS-CoV-2). As May 2024, SARS-CoV-2 has more than 775 million cases and over 7 deaths globally. Despite current vaccination programs, infections are still rapidly increasing, mainly due to appearance spread new variants, variations in immunization rates, limitations vaccines preventing transmission. This underscores need for pan-variant antivirals treatments. interferon (IFN) system is a critical element innate immune response serves as frontline defense against viruses. It induces generalized antiviral state transiently upregulating hundreds IFN-stimulated genes (ISGs). To gain deeper comprehension SARS-CoV-2, its connection COVID-19 pathogenesis, potential therapeutic implications, this review provides detailed overview fundamental aspects diverse ISGs identified their properties SARS-CoV-2. emphasizes importance these proteins controlling viral replication spread. Furthermore, we explore methodological approaches identification conduct comparative analysis with other Deciphering roles interactions pathogens can help identify novel targets therapies enhance our preparedness confront future threats.

Язык: Английский

Процитировано

3
Multi-epitope vaccine against SARS-CoV-2 targeting the spike RBD: an immunoinformatics approach DOI Creative Commons
Yasamin Pahlavan, Omid Yeganeh, Vahid Asghariazar

и другие.

Future Science OA, Год журнала: 2024, Номер 10(1)

Опубликована: Фев. 8, 2024

We designed a SARS-CoV-2 epitope vaccine based on the receptor-binding domain (RBD) in virus spike protein.

Язык: Английский

Процитировано

2
The inflammatory microenvironment of the lung at the time of infection governs innate control of SARS-CoV-2 replication DOI Open Access
Paul J. Baker, Andrea C. Bohrer, Ehydel Castro

и другие.

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

Опубликована: Март 27, 2024

SARS-CoV-2 infection leads to vastly divergent clinical outcomes ranging from asymptomatic fatal disease. Co-morbidities, sex, age, host genetics and vaccine status are known affect disease severity. Yet, how the inflammatory milieu of lung at time exposure impacts control viral replication remains poorly understood. We demonstrate here that immune events in mouse closely preceding significantly impact we identify key innate pathways required limit replication. A diverse set pulmonary stimuli, including resolved antecedent respiratory infections with

Язык: Английский

Процитировано

2