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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptation, Physiological
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Air Microbiology
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Amino Acid Substitution
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Animals
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Birds
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Evolution, Molecular*
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Genetic Fitness
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Glycosylation
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Hemagglutinin Glycoproteins, Influenza Virus / genetics*
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Hemagglutinin Glycoproteins, Influenza Virus / metabolism
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High-Throughput Nucleotide Sequencing
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Humans
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Influenza A Virus, H5N1 Subtype / genetics*
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Influenza A Virus, H5N1 Subtype / pathogenicity*
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Influenza in Birds / virology
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Influenza, Human / immunology
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Influenza, Human / transmission
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Influenza, Human / virology*
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Mammals
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Models, Biological
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Mutation
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Orthomyxoviridae Infections / transmission
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Orthomyxoviridae Infections / virology*
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Probability
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RNA-Dependent RNA Polymerase / genetics*
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Receptors, Virus / metabolism
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Respiratory System / virology*
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Selection, Genetic
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Sialic Acids / metabolism
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Viral Proteins / genetics*
Substances
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Hemagglutinin Glycoproteins, Influenza Virus
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PB2 protein, Influenzavirus A
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Receptors, Virus
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Sialic Acids
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Viral Proteins
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hemagglutinin, avian influenza A virus
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RNA-Dependent RNA Polymerase