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CA Russell, JM Fonville, AE Brown, DF Burke, DL Smith, SL James, S Herfst, S van Boheemen, M Linster, EJ Schrauwen, L Katzelnick, A MosterĂ­n, T Kuiken, E Maher, G Neumann, AD Osterhaus, Y Kawaoka, RA Fouchier and DJ Smith
Abstract
Avian A/H5N1 influenza viruses pose a pandemic threat. As few as five amino acid substitutions, or four with reassortment, might be sufficient for mammal-to-mammal transmission through respiratory droplets. From surveillance data, we found that two of these substitutions are common in A/H5N1 viruses, and thus, some viruses might require only three additional substitutions to become transmissible via respiratory droplets between mammals. We used a mathematical model of within-host virus evolution to study factors that could increase and decrease the probability of the remaining substitutions evolving after the virus has infected a mammalian host. These factors, combined with the presence of some of these substitutions in circulating strains, make a virus evolving in nature a potentially serious threat. These results highlight critical areas in which more data are needed for assessing, and potentially averting, this threat.
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Concepts
Virology, Evolution, Reassortment, Influenza pandemic, Microbiology, Avian influenza, Virus, Influenza
MeSH headings
Adaptation, Physiological, Air Microbiology, Amino Acid Substitution, Animals, Birds, Evolution, Molecular, Genetic Fitness, Glycosylation, Hemagglutinin Glycoproteins, Influenza Virus, High-Throughput Nucleotide Sequencing, Humans, Influenza A Virus, H5N1 Subtype, Influenza in Birds, Influenza, Human, Mammals, Models, Biological, Mutation, Orthomyxoviridae Infections, Probability, RNA Replicase, Receptors, Virus, Respiratory System, Selection, Genetic, Sialic Acids, Viral Proteins
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