In vitro evolution of H5N1 avian influenza virus toward human-type receptor specificity

TY - JOUR

T1 - In vitro evolution of H5N1 avian influenza virus toward human-type receptor specificity

AU - Chen, Li-Mei

AU - Blixt, Klas Ola

AU - Stevens, James

AU - Lipatov, Aleksandr S

AU - Davis, Charles T

AU - Collins, Brian E

AU - Cox, Nancy J

AU - Paulson, James C

AU - Donis, Ruben O

N1 - Published by Elsevier Inc.

PY - 2012/1/5

Y1 - 2012/1/5

N2 - Acquisition of α2-6 sialoside receptor specificity by α2-3 specific highly-pathogenic avian influenza viruses (H5N1) is thought to be a prerequisite for efficient transmission in humans. By in vitro selection for binding α2-6 sialosides, we identified four variant viruses with amino acid substitutions in the hemagglutinin (S227N, D187G, E190G, and Q196R) that revealed modestly increased α2-6 and minimally decreased α2-3 binding by glycan array analysis. However, a mutant virus combining Q196R with mutations from previous pandemic viruses (Q226L and G228S) revealed predominantly α2-6 binding. Unlike the wild type H5N1, this mutant virus was transmitted by direct contact in the ferret model although not by airborne respiratory droplets. However, a reassortant virus with the mutant hemagglutinin, a human N2 neuraminidase and internal genes from an H5N1 virus was partially transmitted via respiratory droplets. The complex changes required for airborne transmissibility in ferrets suggest that extensive evolution is needed for H5N1 transmissibility in humans.

AB - Acquisition of α2-6 sialoside receptor specificity by α2-3 specific highly-pathogenic avian influenza viruses (H5N1) is thought to be a prerequisite for efficient transmission in humans. By in vitro selection for binding α2-6 sialosides, we identified four variant viruses with amino acid substitutions in the hemagglutinin (S227N, D187G, E190G, and Q196R) that revealed modestly increased α2-6 and minimally decreased α2-3 binding by glycan array analysis. However, a mutant virus combining Q196R with mutations from previous pandemic viruses (Q226L and G228S) revealed predominantly α2-6 binding. Unlike the wild type H5N1, this mutant virus was transmitted by direct contact in the ferret model although not by airborne respiratory droplets. However, a reassortant virus with the mutant hemagglutinin, a human N2 neuraminidase and internal genes from an H5N1 virus was partially transmitted via respiratory droplets. The complex changes required for airborne transmissibility in ferrets suggest that extensive evolution is needed for H5N1 transmissibility in humans.

KW - Amino Acid Substitution

KW - Animals

KW - Base Sequence

KW - Chickens

KW - Evolution, Molecular

KW - Ferrets

KW - HEK293 Cells

KW - Hemagglutinin Glycoproteins, Influenza Virus

KW - Humans

KW - Influenza A Virus, H5N1 Subtype

KW - Influenza in Birds

KW - Influenza, Human

KW - Mutation

KW - Neuraminidase

KW - Oligonucleotide Array Sequence Analysis

KW - Polysaccharides

KW - Reassortant Viruses

KW - Receptors, Virus

KW - Sequence Analysis, RNA

U2 - 10.1016/j.virol.2011.10.006

DO - 10.1016/j.virol.2011.10.006

M3 - Journal article

C2 - 22056389

SN - 0042-6822

VL - 422

SP - 105

EP - 113

JO - Virology

JF - Virology

IS - 1

ER -