ArticlePloS one2012
Neurovirulence of H5N1 infection in ferrets is mediated by multifocal replication in distinct permissive neuronal cell regions.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.
- A Systematic Review of the Neuropathologic Findings of Post-Viral Olfactory Dysfunction: Implications and Novel Insight for the COVID-19 Pandemic.American journal of rhinology & allergy · 2021Pooled it
- Review
- Predictive models of influenza A virus lethal disease yield insights from ferret respiratory tract and brain tissues.Scientific reports · 2025Article
- Olfactory immunology: the missing piece in airway and CNS defence.Nature reviews. Immunology · 2024Review
- Olfactory immune response to SARS-CoV-2.Cellular & molecular immunology · 2024Review
- The neuropathogenesis of highly pathogenic avian influenza H5Nx viruses in mammalian species including humans.Trends in neurosciences · 2023Review
- The molecular basis of differential host responses to avian influenza viruses in avian species with differing susceptibility.Frontiers in cellular and infection microbiology · 2023Article
- Mucosal plasma cells are required to protect the upper airway and brain from infection.Immunity · 2022Article
- COVID-19 and cognitive impairment: neuroinvasive and blood‒brain barrier dysfunction.Journal of neuroinflammation · 2022Review
- Nonrespiratory sites of influenza-associated disease: mechanisms and experimental systems for continued study.The FEBS journal · 2022Review
- Article
- Recapitulating influenza virus infection and facilitating antiviral and neuroprotective screening in tractable brain organoids.Theranostics · 2022Article
- In Vivo Models to Study the Pathogenesis of Extra-Respiratory Complications of Influenza A Virus Infection.Viruses · 2021Review
- Shortcut Approaches to Substance Delivery into the Brain Based on Intranasal Administration Using Nanodelivery Strategies for Insulin.Molecules (Basel, Switzerland) · 2020Review
- Characterization of highly pathogenic avian influenza H5Nx viruses in the ferret model.Scientific reports · 2020Article
- Olfactory Dysfunction in Coronavirus Disease 2019 Patients: Observational Cohort Study and Systematic Review.Open forum infectious diseases · 2020Article
- A Guide for the Use of the Ferret Model for Influenza Virus Infection.The American journal of pathology · 2020Review
- Tropism and Infectivity of a Seasonal A(H1N1) and a Highly Pathogenic Avian A(H5N1) Influenza Virus in Primary Differentiated Ferret Nasal Epithelial Cell Cultures.Journal of virology · 2019Article
- Lethal avian influenza A (H5N1) virus replicates in pontomedullary chemosensitive neurons and depresses hypercapnic ventilatory response in mice.American journal of physiology. Lung cellular and molecular physiology · 2019Article
- Programmed Cell Death in the Pathogenesis of Influenza.International journal of molecular sciences · 2018Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Highly pathogenic avian influenza A (HPAI), subtype H5N1, remains an emergent threat to the human population. While respiratory disease is a hallmark of influenza infection, H5N1 has a high incidence of neurological sequelae in many animal species and sporadically in humans. We elucidate the temporal/spatial infection of H5N1 in the brain of ferrets following a low dose, intranasal infection of two HPAI strains of varying neurovirulence and lethality. A/Vietnam/1203/2004 (VN1203) induced mortality in 100% of infected ferrets while A/Hong Kong/483/1997 (HK483) induced lethality in only 20% of ferrets, with death occurring significantly later following infection. Neurological signs were prominent in VN1203 infection, but not HK483, with seizures observed three days post challenge and torticollis or paresis at later time points. VN1203 and HK483 replication kinetics were similar in primary differentiated ferret nasal turbinate cells, and similar viral titers were measured in the nasal turbinates of infected ferrets. Pulmonary viral titers were not different between strains and pathological findings in the lungs were similar in severity. VN1203 replicated to high titers in the olfactory bulb, cerebral cortex, and brain stem; whereas HK483 was not recovered in these tissues. VN1203 was identified adjacent to and within the olfactory nerve tract, and multifocal infection was observed throughout the frontal cortex and cerebrum. VN1203 was also detected throughout the cerebellum, specifically in Purkinje cells and regions that coordinate voluntary movements. These findings suggest the increased lethality of VN1203 in ferrets is due to increased replication in brain regions important in higher order function and explains the neurological signs observed during H5N1 neurovirulence.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.