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.

DNA modification, Influenza virus A, Influenza virus A H5N1, amino acid substitution, animal experiment, animal tissue, antiviral resistance, ferret, hemagglutination test, nonhuman, nose smear, particle size, priority journal, review, sequence analysis, site directed mutagenesis, virus isolation, virus particle, virus replication, virus transmission
dx.doi.org/10.1126/science.1213362, hdl.handle.net/1765/39085
This work was funded by the European Commission 7th Framework Programme; grant id fp7/223498 - European management platform for emerging and re-emerging infectious disease entities (EMPERIE)
Erasmus MC: University Medical Center Rotterdam

Herfst, S, Schrauwen, E.J.A, Linster, M, Chutinimitkul, S, de Wit, E, Munster, V.J, … Fouchier, R.A.M. (2012). Airborne transmission of influenza A/H5N1 virus between ferrets. Science (Vol. 336, pp. 1534–1541). doi:10.1126/science.1213362