The potential for respiratory droplet-transmissible A/H5N1 influenza virus to evolve in a mammalian host.
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.
Department of Zoology, University of Cambridge, Cambridge, UK.
Colin A
CA
Russell
Judith M
JM
Fonville
André E X
AE
Brown
David F
DF
Burke
David L
DL
Smith
Sarah L
SL
James
Sander
S
Herfst
Sander
S
van Boheemen
Martin
M
Linster
Eefje J
EJ
Schrauwen
Leah
L
Katzelnick
Ana
A
Mosterín
Thijs
T
Kuiken
Eileen
E
Maher
Gabriele
G
Neumann
Albert D M E
AD
Osterhaus
Yoshihiro
Y
Kawaoka
Ron A M
RA
Fouchier
Derek J
DJ
Smith
D000222:Adaptation, Physiological; D000391:Air Microbiology; D019943:Amino Acid Substitution; D000818:Animals; D001717:Birds; D019143:Evolution, Molecular; D056084:Genetic Fitness; D006031:Glycosylation; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics* / Q000378:metabolism; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics* / Q000472:pathogenicity*; D005585:Influenza in Birds / Q000821:virology; D007251:Influenza, Human / Q000276:immunology / Q000635:transmission / Q000821:virology*; D008322:Mammals; D008954:Models, Biological; D009154:Mutation; D009976:Orthomyxoviridae Infections / Q000635:transmission / Q000821:virology*; D011336:Probability; D012324:RNA-Dependent RNA Polymerase / Q000235:genetics*; D011991:Receptors, Virus / Q000378:metabolism; D012137:Respiratory System / Q000821:virology*; D012641:Selection, Genetic; D012794:Sialic Acids / Q000378:metabolism; D014764:Viral Proteins / Q000235:genetics*
D019267:Hemagglutinin Glycoproteins, Influenza Virus; C057027:PB2 protein, Influenzavirus A; D011991:Receptors, Virus; D012794:Sialic Acids; D014764:Viral Proteins; C109963:hemagglutinin, avian influenza A virus; D012324:RNA-Dependent RNA Polymerase