Animal Models for Human-Pathogenic Coronavirus and Animal Coronavirus Research

Viruses, Journal Year: 2025, Volume and Issue: 17(1), P. 100 - 100

Published: Jan. 14, 2025

Coronavirus epidemics have posed a serious threat to both human and animal health. To combat emerging infectious diseases caused by coronaviruses, various infection models been developed applied in research, including non-human primate models, ferret hamster mouse others. Moreover, new approaches utilized develop that are more susceptible infection. These include using viral delivery methods induce the expression of receptors tissues employing gene-editing techniques create genetically modified mice. This has led successful establishment for multiple significantly advancing related research. In contrast, livestock pets can be infected coronaviruses provide valuable insights when used as enabling collection accurate clinical data through analysis post-infection pathological features. However, despite potential insights, there is paucity research pertaining these models. this review, we detailed overview recent progress development cause humans animals suggest ways which adapted further enhance their value

Language: Английский

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Severe Acute Respiratory Syndrome Coronavirus 2 Variant Infection Dynamics and Pathogenesis in Transgenic K18-hACE2 and Inbred Immunocompetent C57BL/6J Mice

Viruses, Journal Year: 2025, Volume and Issue: 17(4), P. 500 - 500

Published: March 30, 2025

The global impact of the COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), persists in part due to emergence new variants. Understanding variant-specific infection dynamics and pathogenesis murine models is crucial for identifying phenotypic changes guiding development countermeasures. To address limitations earlier studies that investigated only a few variants or used small sample sizes, we evaluated clinical disease, kinetics, viral titers, cellular localization, histopathologic lungs brains transgenic B6.Cg-Tg(K18-ACE2)2Prlmn/J (“K18”) corresponding genetic control (C57BL/6J) mice expressing human angiotensin-converting enzyme (hACE2). Six SARS-CoV-2 were assessed: B.1 (WA1-like), alpha, beta, delta, omicron, omicron XBB.1.5, using cohorts ≥18 mice. Following intranasal inoculation with B.1, delta variants, K18 experienced rapid weight loss reached euthanasia criteria 5–6 days post-inoculation (dpi). In contrast, inoculated both recovered their starting within 4–6 dpi. Infectious was detected oropharynx at 1 and2 dpi, 2, 4, 6 brain 4 dpi all except omicron. nucleoprotein detected, interstitial pneumonia varying severity observed infected Brain lesions identified As express hACE2 brain—a feature not present humans—we also compared three those mouse-adapted WA1 strain C57BL/6J lacking ACE2 gene. did experience lethal exhibited milder pneumonia, had no evidence neuroinvasion despite similar kinetics These findings demonstrate contrasting phenotypes across two reduced tropism pathology models. This comprehensive analysis mouse provides valuable insights model variant selection future studies.

Language: Английский

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Characterizing a Lethal CAG-ACE2 Transgenic Mouse Model for SARS-CoV-2 infection with Using Cas9-Enhanced Nanopore Sequencing

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

Published: May 31, 2024

Abstract The SARS-CoV-2 pandemic has underscored the necessity for functional transgenic animal models testing. Mouse lines with overexpression of human receptor ACE2 serve as primary model to study COVID-19 infection. Overexpression under a strong ubiquitous promoter facilitates convenient and sensitive testing pathology. We performed pronuclear microinjections using 5 kb CAG-ACE2 linear transgene construct identified three founder 140, 72, 73 copies, respectively. Two these were further analyzed expression profiles sensitivity Both expressed in all organs analyzed. Embryonic fibroblast cell derived from embryos demonstrated severe cytopathic effects following infection, even at low doses (0,1-1.0 TCID 50 ). Infected mice two began show symptoms days post-infection succumbed between 4 7. Histological examination lung tissues terminally ill revealed pathological alterations. To characterize integration site one lines, we applied Nanopore sequencing combined Cas9 enrichment examine internal concatemer structure. Oxford (ONT) is becoming gold standard insert characterization, but it relatively inefficient without targeted region enrichment. digested genomic DNA gRNA against create ends suitable ONT adapter ligation. data analysis that most copies arranged head-to-tail configuration, palindromic junctions being rare. also detected occasional plasmid backbone fragments within concatemer, likely co-purified during gel extraction, which common occurrence microinjections.

Language: Английский

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Characterizing a lethal CAG-ACE2 transgenic mouse model for SARS-CoV-2 infection using Cas9-enhanced nanopore sequencing

Transgenic Research, Journal Year: 2024, Volume and Issue: 33(5), P. 453 - 466

Published: Sept. 25, 2024

Language: Английский

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