Journal
SCIENCE
Volume 336, Issue 6088, Pages 1541-1547Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1222526
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Funding
- University Research Fellowship from the Royal Society
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO) VICI grant
- European Union (EU) FP7 program EMPERIE [223498]
- European Union (EU) FP7 program ANTIGONE [278976]
- Human Frontier Science Program (HFSP) program [P0050/2008]
- Wellcome [087982AIA]
- Bill and Melinda Gates Foundation [OPPGH5383]
- NIH Director's Pioneer Award [DP1-OD000490-01]
- National Institute of Allergy and Infectious Diseases (NIAID)-NIH [HHSN266200700010C.]
- NIAID-NIH [R01 AI 069274]
- Ministry of Education, Culture, Sports, Science, and Technology of Japan
- ERATO
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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.
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