Neurovirulence of H5N1 Infection in Ferrets Is Mediated by Multifocal Replication in Distinct Permissive Neuronal Cell Regions

Autor: Sarah E. Vaughan, John Pyles, Kevin S. Harrod, Jennifer R. Plourde, R. Colby Layton, Jennifer L. Tipper
Rok vydání: 2012
Předmět:
Central Nervous System
Male
Pathology
Anatomy and Physiology
Respiratory System
lcsh:Medicine
Neuroinvasiveness
Pathogenesis
Virus Replication
medicine.disease_cause
Olfactory nerve
Emerging Viral Diseases
Influenza A virus
lcsh:Science
education.field_of_study
Multidisciplinary
Virulence
Cerebrum
virus diseases
Immunohistochemistry
medicine.anatomical_structure
Medicine
Research Article
medicine.medical_specialty
Neurovirulence
Population
Central nervous system
Biology
Real-Time Polymerase Chain Reaction
Microbiology
Orthomyxoviridae Infections
Virology
medicine
Animals
Respiratory Physiology
education
Influenza A Virus
H5N1 Subtype
lcsh:R
Ferrets
Viral Replication
Olfactory bulb
Animal Models of Infection
Viral Disease Diagnosis
Emerging Infectious Diseases
Viral replication
lcsh:Q
Nasal concha
Viral Transmission and Infection
Zdroj: PLoS ONE
PLoS ONE, Vol 7, Iss 10, p e46605 (2012)
ISSN: 1932-6203
Popis: 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.
Databáze: OpenAIRE
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