The Potential for Respiratory Droplet-Transmissible A/H5N1 Influenza Virus to Evolve in a Mammalian Host

• Published in: Science (American Association for the Advancement of Science) Vol. 336; no. 6088; pp. 1541 - 1547
• Main Authors: Russell, Colin A., Fonville, Judith M., Brown, André E. X., Burke, David F., Smith, David L., James, Sarah L., Herfst, Sander, van Boheemen, Sander, Linster, Martin, Schrauwen, Eefje J., Katzelnick, Leah, Mosterín, Ana, Kuiken, Thijs, Maher, Eileen, Neumann, Gabriele, Osterhaus, Albert D. M. E., Kawaoka, Yoshihiro, Fouchier, Ron A. M., Smith, Derek J.
• Format: Journal Article
• Language: English
• Published: United States American Association for the Advancement of Science 22.06.2012; The American Association for the Advancement of Science
• Subjects: Adaptation, Physiological; Air Microbiology; Amino Acid Substitution; Amino acids; Animals; Avian flu; Birds; Circulating; Disease transmission; Droplets; Evolution; Evolution, Molecular; Genetic Fitness; Genetic mutation; Glycosylation; Hemagglutinin Glycoproteins, Influenza Virus - genetics; Hemagglutinin Glycoproteins, Influenza Virus - metabolism; High-Throughput Nucleotide Sequencing; Humans; Infections; Influenza; Influenza A Virus, H5N1 Subtype - genetics; Influenza A Virus, H5N1 Subtype - pathogenicity; Influenza in Birds - virology; Influenza virus; Influenza, Human - immunology; Influenza, Human - transmission; Influenza, Human - virology; Mammals; Mathematical models; Models, Biological; Mutation; Nucleotides; Orthomyxoviridae; Orthomyxoviridae Infections - transmission; Orthomyxoviridae Infections - virology; Probability; Receptors, Virus - metabolism; Respiratory System - virology; RNA-Dependent RNA Polymerase - genetics; Selection, Genetic; Sequencing; Sialic Acids - metabolism; Surveillance; Viral Proteins - genetics; Virions; Viruses
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1222526

Avian A/H5N1 influenza viruses pose a pandemic threat. As few as five amino acid substitutions, or four with reassortaient, 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.