Effect of receptor binding domain mutations on receptor binding and transmissibility of avian influenza H5N1 viruses

Taronna R Maines; Li-Mei Chen; Neal Van Hoeven; Terrence M Tumpey; Ola Blixt; Jessica A Belser; Kortney M Gustin; Melissa B Pearce; Claudia Pappas; James Stevens; Nancy J Cox; James C Paulson; Rahul Raman; Ram Sasisekharan; Jacqueline M Katz; Ruben O Donis

doi:10.1016/j.virol.2011.02.015

Effect of receptor binding domain mutations on receptor binding and transmissibility of avian influenza H5N1 viruses

Taronna R Maines, Li-Mei Chen, Neal Van Hoeven, Terrence M Tumpey, Ola Blixt, Jessica A Belser, Kortney M Gustin, Melissa B Pearce, Claudia Pappas, James Stevens, Nancy J Cox, James C Paulson, Rahul Raman, Ram Sasisekharan, Jacqueline M Katz, Ruben O Donis

Glycomics Program

84 Citations (Scopus)

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.

Original language	English
Journal	Future Virology
Volume	413
Issue number	1
Pages (from-to)	139-47
Number of pages	9
ISSN	1746-0794
DOIs	https://doi.org/10.1016/j.virol.2011.02.015
Publication status	Published - 25 Apr 2011

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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. Future Virology, 413(1), 139-47. https://doi.org/10.1016/j.virol.2011.02.015

Maines, TR, Chen, L-M, Van Hoeven, N, Tumpey, TM, Blixt, O, Belser, JA, Gustin, KM, Pearce, MB, Pappas, C, Stevens, J, Cox, NJ, Paulson, JC, Raman, R, Sasisekharan, R, Katz, JM & Donis, RO 2011, 'Effect of receptor binding domain mutations on receptor binding and transmissibility of avian influenza H5N1 viruses', Future Virology, vol. 413, no. 1, pp. 139-47. https://doi.org/10.1016/j.virol.2011.02.015

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title = "Effect of receptor binding domain mutations on receptor binding and transmissibility of avian influenza H5N1 viruses",

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.",

author = "Maines, {Taronna R} and Li-Mei Chen and {Van Hoeven}, Neal and Tumpey, {Terrence M} and Ola Blixt and Belser, {Jessica A} and Gustin, {Kortney M} and Pearce, {Melissa B} and Claudia Pappas and James Stevens and Cox, {Nancy J} and Paulson, {James C} and Rahul Raman and Ram Sasisekharan and Katz, {Jacqueline M} and Donis, {Ruben O}",

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AU - Maines, Taronna R

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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

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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.

AB - 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.

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JO - Future Virology

JF - Future Virology

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Effect of receptor binding domain mutations on receptor binding and transmissibility of avian influenza H5N1 viruses

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