Fc-mediated pan-sarbecovirus protection after alphavirus vector vaccination

Cell Reports, Год журнала: 2023, Номер 42(4), С. 112326 - 112326

Опубликована: Март 30, 2023

Group 2B β-coronaviruses (sarbecoviruses) have caused regional and global epidemics in modern history. Here, we evaluate the mechanisms of cross-sarbecovirus protective immunity, currently less clear yet important for pan-sarbecovirus vaccine development, using a panel alphavirus-vectored vaccines covering bat to human strains. While vaccination does not prevent virus replication, it protects against lethal heterologous disease outcomes both severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) clade sarbecovirus challenge models. The spike tested primarily elicit highly S1-specific homologous neutralizing antibody response with no detectable cross-virus neutralization. Rather, non-neutralizing functions, mechanistically linked FcgR4 S2, mediate cross-protection wild-type mice. Protection is lost FcR knockout mice, further supporting model non-neutralizing, antibodies. These data highlight importance FcR-mediated cross-protective immune responses universal designs.

Язык: Английский

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Gut‐lung axis and asthma: A historical review on mechanism and future perspective

Clinical and Translational Allergy, Год журнала: 2024, Номер 14(5)

Опубликована: Апрель 30, 2024

Abstract Background Gut microbiota are closely related to the development and regulation of host immune system by regulating maturation cells resistance pathogens, which affects immunity. Early use antibiotics disrupts homeostasis gut increases risk asthma. actively interact with via gut‐lung axis, a bidirectional communication pathway between lung. The manipulation through probiotics, helminth therapy, fecal transplantation (FMT) combat asthma has become hot research topic. Body This review mainly describes current pathogenesis asthma, role axis in Moreover, potential manipulating its metabolites as treatment strategy for been discussed. Conclusion effect on microecology imbalance contributes bacterial structural components metabolites. Asthma, turn, can also cause intestinal damage inflammation throughout body. FMT inform strategies pathogens.

Язык: Английский

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Mapping of susceptibility loci for Ebola virus pathogenesis in mice

Cell Reports, Год журнала: 2024, Номер 43(5), С. 114127 - 114127

Опубликована: Апрель 21, 2024

Ebola virus (EBOV), a major global health concern, causes severe, often fatal EBOV disease (EVD) in humans. Host genetic variation plays critical role, yet the identity of host susceptibility loci mammals remains unknown. Using reference populations, we generate an F2 mapping cohort to identify that regulate EVD. While disease-resistant mice display minimal pathogenesis, susceptible severe liver pathology consistent with EVD-like and transcriptional signatures associated inflammatory metabolic processes. A significant quantitative trait locus (QTL) for RNA load blood is identified chromosome (chr)8, clinical mortality QTL mapped chr7, which includes Trim5 locus. knockout mice, validate as one potential driver failure after infection. The identification provides insight into molecular mechanisms regulating EVD progression severity, potentially informing therapeutics vaccination strategies.

Язык: Английский

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Genetic loci regulate Sarbecovirus pathogenesis: A comparison across mice and humans

Virus Research, Год журнала: 2024, Номер 344, С. 199357 - 199357

Опубликована: Март 23, 2024

Coronavirus (CoV) cause considerable morbidity and mortality in humans other mammals, as evidenced by the emergence of Severe Acute Respiratory CoV (SARS-CoV) 2003, Middle East (MERS-CoV) 2012, SARS-CoV-2 2019. Although poorly characterized, natural genetic variation human mammals modulate virus pathogenesis, reflected spectrum clinical outcomes ranging from asymptomatic infections to lethal disease. Using multiple epidemic zoonotic Sarbecoviruses, coupled with murine Collaborative Cross reference populations, we identify several dozen quantitative trait loci that regulate SARS-like group-2B pathogenesis replication. Under a Chr4 QTL, deleted candidate interferon stimulated gene, Trim14 which resulted enhanced SARS-CoV titers disease, suggesting an antiviral role during infection. Importantly, about 60 % QTL encode susceptibility genes identified priority candidates genome-wide association studies (GWAS) after infection, similar selective forces have targeted analogous pathways Sarbecovirus disease across diverse mammalian hosts. These provide experimental platform rodents investigate molecular-genetic mechanisms potential cross type-specific cross-SARS-like group 2B replication, immunity, rodent models. Our study also provides paradigm for identifying highly heterogeneous virulent viruses sporadically emerge reservoirs plague animal populations.

Язык: Английский

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Animal models of Long Covid: A hit-and-run disease

Science Translational Medicine, Год журнала: 2024, Номер 16(773)

Опубликована: Ноя. 13, 2024

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV 2) pandemic has caused more than 7 million deaths globally. Despite the presence of infection- and vaccine-induced immunity, SARS-CoV-2 infections remain a major global health concern because emergence variants that can cause disease 2019 (COVID-19) or enhance Long Covid phenotypes. About 5 to 10% SARS-CoV-2-infected individuals develop Covid, which, similar COVID 19, often affects lung. However, also affect other peripheral organs, especially brain. causal relationships between phenotypes, long-term symptoms, involvement multiple organ systems elusive, animal model mimicking both post-acute phases are imperative. Here, we review current state models, including possible future applications.

Язык: Английский

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Considering innate immune responses in SARS-CoV-2 infection and COVID-19

Nature reviews. Immunology, Год журнала: 2022, Номер 22(8), С. 465 - 470

Опубликована: Июль 4, 2022

Язык: Английский

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Host genetic variation guides hepacivirus clearance, chronicity, and liver fibrosis in mice

Hepatology, Год журнала: 2023, Номер 79(1), С. 183 - 197

Опубликована: Авг. 4, 2023

Background & Aims: Human genetic variation is thought to guide the outcome of HCV infection, but model systems within which dissect these host mechanisms are limited. Norway rat hepacivirus, closely related HCV, causes chronic liver infection in rats acute self-limiting hepatitis typical strains laboratory mice, resolves 2 weeks. The Collaborative Cross (CC) a robust mouse genetics resource comprised panel recombinant inbred strains, complexity human genome and provide system understand diseases driven by complex allelic variation. Approach Results: We infected CC with hepacivirus identified several that failed clear virus after 4 Strains displayed an array virologic phenotypes ranging from delayed clearance (CC046) chronicity (CC071, CC080) viremia for at least 10 months. Body weight loss, hepatocyte frequency, viral evolution, T-cell recruitment liver, inflammation, capacity develop fibrosis varied among strains. Conclusions: These models recapitulate many aspects humans demonstrate affects multitude viruses phenotypes. can be used better molecular drive chronicity, interactions promote disease manifestations like fibrosis, therapeutic vaccine performance, how factors affected

Язык: Английский

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Host Genetic Variation Impacts SARS-CoV-2 Vaccination Response in the Diversity Outbred Mouse Population

Vaccines, Год журнала: 2024, Номер 12(1), С. 103 - 103

Опубликована: Янв. 20, 2024

The COVID-19 pandemic led to the rapid and worldwide development of highly effective vaccines against SARS-CoV-2. However, there is significant individual-to-individual variation in vaccine efficacy due factors including viral variants, host age, immune status, environmental genetic factors. Understanding those determinants driving this may inform more broadly protective strategies. While are known impact for respiratory pathogens such as influenza tuberculosis, on not well understood. To model SARS-CoV-2 efficacy, while controlling non-genetic factors, we used Diversity Outbred (DO) mouse model. We found that DO mice immunized exhibited high levels vaccine-induced neutralizing antibody responses. majority vaccinated were protected from virus-induced disease, similar human populations, observed breakthrough a subset mice. Importantly, antibody, titer heritable, indicating serves useful system studying contribution both disease outcomes.

Язык: Английский

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Host genetic diversity contributes to disease outcome in Crimean-Congo hemorrhagic fever virus infection

npj Viruses, Год журнала: 2025, Номер 3(1)

Опубликована: Фев. 27, 2025

Abstract The Crimean-Congo hemorrhagic fever virus (CCHFV) causes (CCHF), a widely distributed disease with significant morbidity and mortality. has high genetic diversity correlated geographic distribution but limited temporal evolution within regions. Despite this, cases of CCHF region present as spectrum from often unrecognized asymptomatic infections to severe, fatal viral fever, suggesting host factors may play role in outcome. We investigated the effect on outcome CCHFV infection genetically diverse Collaborative cross (CC)-mouse model. Infected mice recapitulated full recognized humans, similar human disease, replication, tissue pathology, inflammatory responses were associated severity. Our study demonstrates that genetics contribute establishes CC mouse resource model understand how contributes

Язык: Английский

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Unique immune profiles in collaborative cross mice linked to survival and viral clearance upon infection

iScience, Год журнала: 2024, Номер 27(3), С. 109103 - 109103

Опубликована: Фев. 2, 2024

The response to infection is generally heterogeneous and diverse, with some individuals remaining asymptomatic while others present severe disease or a diverse range of symptoms. Here, we address the role host genetics on immune phenotypes clinical outcomes following viral by studying genetically mice from Collaborative Cross (CC), allowing for use small animal model controlled genetic diversity maintaining replicates. We demonstrate variation deeply profiling broad innate adaptive cell at steady-state in 63 distinct CC mouse strains link baseline signatures virologic herpes simplex virus 2 (HSV-2) acute respiratory syndrome coronavirus (SARS-CoV-2). This work serves as resource strain selection based presentation upon infection, further, points possible pre-infection correlates survival early clearance infection.

Язык: Английский

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