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Effect of receptor binding domain mutations on receptor binding and transmissibility of avian influenza H5N1 viruses.
Virology. 2011 Apr 25; 413(1):139-47.V

Abstract

Although H5N1 influenza viruses have been responsible for hundreds of human infections, these avian influenza viruses have not fully adapted to the human host. The lack of sustained transmission in humans may be due, in part, to their avian-like receptor preference. Here, we have introduced receptor binding domain mutations within the hemagglutinin (HA) gene of two H5N1 viruses and evaluated changes in receptor binding specificity by glycan microarray analysis. The impact of these mutations on replication efficiency was assessed in vitro and in vivo. Although certain mutations switched the receptor binding preference of the H5 HA, the rescued mutant viruses displayed reduced replication in vitro and delayed peak virus shedding in ferrets. An improvement in transmission efficiency was not observed with any of the mutants compared to the parental viruses, indicating that alternative molecular changes are required for H5N1 viruses to fully adapt to humans and to acquire pandemic capability.

Authors+Show Affiliations

Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control & Prevention, 1600 Clifton Road, MS-G16, Atlanta, GA 30333, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21397290

Citation

Maines, Taronna R., et al. "Effect of Receptor Binding Domain Mutations On Receptor Binding and Transmissibility of Avian Influenza H5N1 Viruses." Virology, vol. 413, no. 1, 2011, pp. 139-47.
Maines TR, Chen LM, Van Hoeven N, et al. Effect of receptor binding domain mutations on receptor binding and transmissibility of avian influenza H5N1 viruses. Virology. 2011;413(1):139-47.
Maines, T. R., Chen, L. M., Van Hoeven, N., Tumpey, T. M., Blixt, O., Belser, J. A., Gustin, K. M., Pearce, M. B., Pappas, C., Stevens, J., Cox, N. J., Paulson, J. C., Raman, R., Sasisekharan, R., Katz, J. M., & Donis, R. O. (2011). Effect of receptor binding domain mutations on receptor binding and transmissibility of avian influenza H5N1 viruses. Virology, 413(1), 139-47. https://doi.org/10.1016/j.virol.2011.02.015
Maines TR, et al. Effect of Receptor Binding Domain Mutations On Receptor Binding and Transmissibility of Avian Influenza H5N1 Viruses. Virology. 2011 Apr 25;413(1):139-47. PubMed PMID: 21397290.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of receptor binding domain mutations on receptor binding and transmissibility of avian influenza H5N1 viruses. AU - Maines,Taronna R, AU - Chen,Li-Mei, AU - Van Hoeven,Neal, AU - Tumpey,Terrence M, AU - Blixt,Ola, AU - Belser,Jessica A, AU - Gustin,Kortney M, AU - Pearce,Melissa B, AU - Pappas,Claudia, AU - Stevens,James, AU - Cox,Nancy J, AU - Paulson,James C, AU - Raman,Rahul, AU - Sasisekharan,Ram, AU - Katz,Jacqueline M, AU - Donis,Ruben O, Y1 - 2011/03/23/ PY - 2010/11/22/received PY - 2010/12/28/revised PY - 2011/02/11/accepted PY - 2011/3/15/entrez PY - 2011/3/15/pubmed PY - 2011/6/3/medline SP - 139 EP - 47 JF - Virology JO - Virology VL - 413 IS - 1 N2 - Although H5N1 influenza viruses have been responsible for hundreds of human infections, these avian influenza viruses have not fully adapted to the human host. The lack of sustained transmission in humans may be due, in part, to their avian-like receptor preference. Here, we have introduced receptor binding domain mutations within the hemagglutinin (HA) gene of two H5N1 viruses and evaluated changes in receptor binding specificity by glycan microarray analysis. The impact of these mutations on replication efficiency was assessed in vitro and in vivo. Although certain mutations switched the receptor binding preference of the H5 HA, the rescued mutant viruses displayed reduced replication in vitro and delayed peak virus shedding in ferrets. An improvement in transmission efficiency was not observed with any of the mutants compared to the parental viruses, indicating that alternative molecular changes are required for H5N1 viruses to fully adapt to humans and to acquire pandemic capability. SN - 1096-0341 UR - https://www.unboundmedicine.com/medline/citation/21397290/Effect_of_receptor_binding_domain_mutations_on_receptor_binding_and_transmissibility_of_avian_influenza_H5N1_viruses_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0042-6822(11)00076-6 DB - PRIME DP - Unbound Medicine ER -