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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
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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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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