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.

Influenza virus A H5N1, amino acid sequence, amino acid substitution, antiviral resistance, gene mutation, glycosylation, human, immune response, mathematical model, nonhuman, phylogenetic tree, priority journal, review, sequence analysis, virion, virus load, virus replication, virus transmission
dx.doi.org/10.1126/science.1222526, hdl.handle.net/1765/39084
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), This work was funded by the European Commission 7th Framework Programme; grant id fp7/278976 - ANTIcipating the Global Onset of Novel Epidemics (ANTIGONE)
Erasmus MC: University Medical Center Rotterdam

Russell, C.A, Fonville, J.M, Brown, A.E.X, Burke, D.F, Smith, D.L, James, S.L, … Fouchier, R.A.M. (2012). The potential for respiratory droplet-transmissible A/H5N1 influenza virus to evolve in a mammalian host. Science (Vol. 336, pp. 1541–1547). doi:10.1126/science.1222526