ArticlePLoS pathogens2023
Evolution of highly pathogenic H5N1 influenza A virus in the central nervous system of ferrets.
Article in PLoS pathogens, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 29 citations in OpenAlex.
- Increased or decreased numbers of CpG dinucleotide motifs in the genome of influenza A virus do not affectJournal of virology · 2026Article
- Intranasal infection of Rift Valley fever virus in the ferret model suggests multiple routes of neuroinvasion with consequential encephalitis and ophthalmitis.Scientific reports · 2026Article
- On the brink of emergence: an evolutionary approach to Influenza A virus H5N1 isolated from humans.Virus research · 2026Article
- Olfactory immunity: defending the neural-mucosal barrier.Journal of immunology (Baltimore, Md. : 1950) · 2026Review
- Potent efficacy of an NA-targeting antibody against a broad spectrum of H5N1 influenza viruses.Nature communications · 2026Article
- Fatal H5N1 Highly Pathogenic Avian Influenza with Retrograde Neuroinvasion in a Free-Ranging Leopard Cat (Animals : an open access journal from MDPI · 2026Article
- PB1 mutations as key drivers of influenza A virus evolution.Frontiers in microbiology · 2026Review
- Controlled human influenza infection reveals heterogeneous expulsion of infectious virus into air.medRxiv : the preprint server for health sciences · 2025Article
- PB2 and NP of North American H5N1 virus drive immune cell replication and systemic infections.Science advances · 2025Article
- Predictive models of influenza A virus lethal disease yield insights from ferret respiratory tract and brain tissues.Scientific reports · 2025Article
- Transmission and pathogenicity in ferrets after experimental infection with HPAI clade 2.3.4.4b H5N1 viruses.The Journal of general virology · 2025Article
- Clade 2.3.4.4b highly pathogenic avian influenza H5N1 viruses: knowns, unknowns, and challenges.Journal of virology · 2025Review
- Evolution takes multiple paths to evolvability when facing environmental change.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Emerging threats of H5N1 clade 2.3.4.4b: cross-species transmission, pathogenesis, and pandemic risk.Frontiers in cellular and infection microbiology · 2025Review
- Are we cultivating the perfect storm for a human avian influenza pandemic?Biological research · 2024Review
- Review
- Highly pathogenic avian influenza (HPAI) H5 virus exposure in domestic cats and rural stray cats, the Netherlands, October 2020 to June 2023.Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin · 2024Article
- Modulation of human-to-swine influenza a virus adaptation by the neuraminidase low-affinity calcium-binding pocket.Communications biology · 2024Article
- Highly pathogenic avian influenza A(H5N1) virus in a common bottlenose dolphin (Tursiops truncatus) in Florida.Communications biology · 2024Article
- Exploring associations between viral titer measurements and disease outcomes in ferrets inoculated with 125 contemporary influenza A viruses.Journal of virology · 2024Article
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Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
Abstract
Central nervous system (CNS) disease is the most common extra-respiratory tract complication of influenza A virus infections in humans. Remarkably, zoonotic highly pathogenic avian influenza (HPAI) H5N1 virus infections are more often associated with CNS disease than infections with seasonal influenza viruses. Evolution of avian influenza viruses has been extensively studied in the context of respiratory infections, but evolutionary processes in CNS infections remain poorly understood. We have previously observed that the ability of HPAI A/Indonesia/5/2005 (H5N1) virus to replicate in and spread throughout the CNS varies widely between individual ferrets. Based on these observations, we sought to understand the impact of entrance into and replication within the CNS on the evolutionary dynamics of virus populations. First, we identified and characterized three substitutions-PB1 E177G and A652T and NP I119M - detected in the CNS of a ferret infected with influenza A/Indonesia/5/2005 (H5N1) virus that developed a severe meningo-encephalitis. We found that some of these substitutions, individually or collectively, resulted in increased polymerase activity in vitro. Nevertheless, in vivo, the virus bearing the CNS-associated mutations retained its capacity to infect the CNS but showed reduced dispersion to other anatomical sites. Analyses of viral diversity in the nasal turbinate and olfactory bulb revealed the lack of a genetic bottleneck acting on virus populations accessing the CNS via this route. Furthermore, virus populations bearing the CNS-associated mutations showed signs of positive selection in the brainstem. These features of dispersion to the CNS are consistent with the action of selective processes, underlining the potential for H5N1 viruses to adapt to the CNS.
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