Airborne transmission of influenza A/H5N1 virus between ferrets.
Highly pathogenic avian influenza A/H5N1 virus can cause morbidity and mortality in humans but thus far has not acquired the ability to be transmitted by aerosol or respiratory droplet ("airborne transmission") between humans. To address the concern that the virus could acquire this ability under natural conditions, we genetically modified A/H5N1 virus by site-directed mutagenesis and subsequent serial passage in ferrets. The genetically modified A/H5N1 virus acquired mutations during passage in ferrets, ultimately becoming airborne transmissible in ferrets. None of the recipient ferrets died after airborne infection with the mutant A/H5N1 viruses. Four amino acid substitutions in the host receptor-binding protein hemagglutinin, and one in the polymerase complex protein basic polymerase 2, were consistently present in airborne-transmitted viruses. The transmissible viruses were sensitive to the antiviral drug oseltamivir and reacted well with antisera raised against H5 influenza vaccine strains. Thus, avian A/H5N1 influenza viruses can acquire the capacity for airborne transmission between mammals without recombination in an intermediate host and therefore constitute a risk for human pandemic influenza.
Department of Virology, Erasmus Medical Center, Rotterdam, The Netherlands.
Sander
S
Herfst
Eefje J A
EJ
Schrauwen
Martin
M
Linster
Salin
S
Chutinimitkul
Emmie
E
de Wit
Vincent J
VJ
Munster
Erin M
EM
Sorrell
Theo M
TM
Bestebroer
David F
DF
Burke
Derek J
DJ
Smith
Guus F
GF
Rimmelzwaan
Albert D M E
AD
Osterhaus
Ron A M
RA
Fouchier
D000391:Air Microbiology; D019943:Amino Acid Substitution; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D003264:Containment of Biohazards; D004195:Disease Models, Animal; D005260:Female; D005289:Ferrets; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007106:Immune Sera; D053124:Influenza A Virus, H5N1 Subtype / Q000187:drug effects / Q000235:genetics* / Q000472:pathogenicity* / Q000502:physiology; D005585:Influenza in Birds / Q000453:epidemiology / Q000821:virology; D007251:Influenza, Human / Q000453:epidemiology / Q000635:transmission / Q000821:virology*; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D009976:Orthomyxoviridae Infections / Q000635:transmission / Q000821:virology*; D053139:Oseltamivir / Q000494:pharmacology; D058873:Pandemics; D011200:Poultry; D012324:RNA-Dependent RNA Polymerase / Q000737:chemistry / Q000235:genetics; D016865:Reassortant Viruses / Q000472:pathogenicity; D011991:Receptors, Virus / Q000378:metabolism; D012137:Respiratory System / Q000821:virology*; D059386:Reverse Genetics; D012692:Serial Passage; D012794:Sialic Acids / Q000378:metabolism; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics; D014774:Virulence; D014779:Virus Replication; D017201:Virus Shedding
D000998:Antiviral Agents; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007106:Immune Sera; C057027:PB2 protein, Influenzavirus A; D011991:Receptors, Virus; D012794:Sialic Acids; D014764:Viral Proteins; C109963:hemagglutinin, avian influenza A virus; D053139:Oseltamivir; D012324:RNA-Dependent RNA Polymerase