Tags

Type your tag names separated by a space and hit enter

Identification, characterization, and natural selection of mutations driving airborne transmission of A/H5N1 virus.
Cell. 2014 Apr 10; 157(2):329-339.Cell

Abstract

Recently, A/H5N1 influenza viruses were shown to acquire airborne transmissibility between ferrets upon targeted mutagenesis and virus passage. The critical genetic changes in airborne A/Indonesia/5/05 were not yet identified. Here, five substitutions proved to be sufficient to determine this airborne transmission phenotype. Substitutions in PB1 and PB2 collectively caused enhanced transcription and virus replication. One substitution increased HA thermostability and lowered the pH of membrane fusion. Two substitutions independently changed HA binding preference from α2,3-linked to α2,6-linked sialic acid receptors. The loss of a glycosylation site in HA enhanced overall binding to receptors. The acquired substitutions emerged early during ferret passage as minor variants and became dominant rapidly. Identification of substitutions that are essential for airborne transmission of avian influenza viruses between ferrets and their associated phenotypes advances our fundamental understanding of virus transmission and will increase the value of future surveillance programs and public health risk assessments.

Authors+Show Affiliations

Department of Viroscience, Postgraduate School of Molecular Medicine, Erasmus Medical Center, 3015GE Rotterdam, the Netherlands.Department of Viroscience, Postgraduate School of Molecular Medicine, Erasmus Medical Center, 3015GE Rotterdam, the Netherlands.Department of Viroscience, Postgraduate School of Molecular Medicine, Erasmus Medical Center, 3015GE Rotterdam, the Netherlands.Department of Viroscience, Postgraduate School of Molecular Medicine, Erasmus Medical Center, 3015GE Rotterdam, the Netherlands.Department of Viroscience, Postgraduate School of Molecular Medicine, Erasmus Medical Center, 3015GE Rotterdam, the Netherlands.Department of Viroscience, Postgraduate School of Molecular Medicine, Erasmus Medical Center, 3015GE Rotterdam, the Netherlands.Department of Viroscience, Postgraduate School of Molecular Medicine, Erasmus Medical Center, 3015GE Rotterdam, the Netherlands.Institute of Virology, Philipps-University, 35043 Marburg, Germany.Department of Viroscience, Postgraduate School of Molecular Medicine, Erasmus Medical Center, 3015GE Rotterdam, the Netherlands.Department of Viroscience, Postgraduate School of Molecular Medicine, Erasmus Medical Center, 3015GE Rotterdam, the Netherlands.Department of Viroscience, Postgraduate School of Molecular Medicine, Erasmus Medical Center, 3015GE Rotterdam, the Netherlands.Institute of Virology, Philipps-University, 35043 Marburg, Germany.Department of Viroscience, Postgraduate School of Molecular Medicine, Erasmus Medical Center, 3015GE Rotterdam, the Netherlands. Electronic address: r.fouchier@erasmusmc.nl.Department of Viroscience, Postgraduate School of Molecular Medicine, Erasmus Medical Center, 3015GE Rotterdam, the Netherlands.

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

24725402

Citation

Linster, Martin, et al. "Identification, Characterization, and Natural Selection of Mutations Driving Airborne Transmission of A/H5N1 Virus." Cell, vol. 157, no. 2, 2014, pp. 329-339.
Linster M, van Boheemen S, de Graaf M, et al. Identification, characterization, and natural selection of mutations driving airborne transmission of A/H5N1 virus. Cell. 2014;157(2):329-339.
Linster, M., van Boheemen, S., de Graaf, M., Schrauwen, E. J. A., Lexmond, P., Mänz, B., Bestebroer, T. M., Baumann, J., van Riel, D., Rimmelzwaan, G. F., Osterhaus, A. D. M. E., Matrosovich, M., Fouchier, R. A. M., & Herfst, S. (2014). Identification, characterization, and natural selection of mutations driving airborne transmission of A/H5N1 virus. Cell, 157(2), 329-339. https://doi.org/10.1016/j.cell.2014.02.040
Linster M, et al. Identification, Characterization, and Natural Selection of Mutations Driving Airborne Transmission of A/H5N1 Virus. Cell. 2014 Apr 10;157(2):329-339. PubMed PMID: 24725402.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Identification, characterization, and natural selection of mutations driving airborne transmission of A/H5N1 virus. AU - Linster,Martin, AU - van Boheemen,Sander, AU - de Graaf,Miranda, AU - Schrauwen,Eefje J A, AU - Lexmond,Pascal, AU - Mänz,Benjamin, AU - Bestebroer,Theo M, AU - Baumann,Jan, AU - van Riel,Debby, AU - Rimmelzwaan,Guus F, AU - Osterhaus,Albert D M E, AU - Matrosovich,Mikhail, AU - Fouchier,Ron A M, AU - Herfst,Sander, PY - 2013/11/26/received PY - 2014/02/17/revised PY - 2014/02/24/accepted PY - 2014/4/15/entrez PY - 2014/4/15/pubmed PY - 2014/7/18/medline SP - 329 EP - 339 JF - Cell JO - Cell VL - 157 IS - 2 N2 - Recently, A/H5N1 influenza viruses were shown to acquire airborne transmissibility between ferrets upon targeted mutagenesis and virus passage. The critical genetic changes in airborne A/Indonesia/5/05 were not yet identified. Here, five substitutions proved to be sufficient to determine this airborne transmission phenotype. Substitutions in PB1 and PB2 collectively caused enhanced transcription and virus replication. One substitution increased HA thermostability and lowered the pH of membrane fusion. Two substitutions independently changed HA binding preference from α2,3-linked to α2,6-linked sialic acid receptors. The loss of a glycosylation site in HA enhanced overall binding to receptors. The acquired substitutions emerged early during ferret passage as minor variants and became dominant rapidly. Identification of substitutions that are essential for airborne transmission of avian influenza viruses between ferrets and their associated phenotypes advances our fundamental understanding of virus transmission and will increase the value of future surveillance programs and public health risk assessments. SN - 1097-4172 UR - https://www.unboundmedicine.com/medline/citation/24725402/Identification_characterization_and_natural_selection_of_mutations_driving_airborne_transmission_of_A/H5N1_virus_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0092-8674(14)00281-5 DB - PRIME DP - Unbound Medicine ER -