title: The roles of hemagglutinin Phe-95 in receptor binding and pathogenicity of influenza B virus.
abstract: Diverged ~4000 years ago, influenza B virus has several important differences from influenza A virus, including lower receptor-binding affinity and highly restricted host range. Based on our prior structural studies, we hypothesized that a single-residue difference in the receptor-binding site of hemagglutinin (HA), Phe-95 in influenza B virus versus Tyr-98 in influenza A/H1-H15, is possibly a key determinant for the low receptor-binding affinity. Here we demonstrate that the mutation Phe95→Tyr in influenza B virus HA restores all three hydrogen bonds made by Tyr-98 in influenza A/H1-15 HA and has the potential to enhance receptor binding. However, the full realization of this potential is influenced by the local environment into which the mutation is introduced. The binding and replication of the recombinant viruses correlate well with the receptor-binding capabilities of HA. These results are discussed in relation to the roles of Phe-95 in receptor binding and pathogenicity of influenza B virus.
authors: Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Department of Bioengineering, Rice University, 6100 Main Street, Houston, TX 77005, USA.
authors: Fengyun
authors: F
authors: Ni
authors: Department of Molecular Virology and Microbiology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
authors: Innocent Nnadi
authors: IN
authors: Mbawuike
authors: Life Sciences Collaborative Access Team (LS-CAT), Synchrotron Research Center, Northwestern University, Argonne, IL 60439, USA.
authors: Elena
authors: E
authors: Kondrashkina
authors: Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA. Electronic address: qinghuaw@bcm.edu.
authors: Qinghua
authors: Q
authors: Wang
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D005260:Female; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009980:Influenza A virus / Q000235:genetics / Q000378:metabolism; D009981:Influenza B virus / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D008807:Mice, Inbred BALB C; D008958:Models, Molecular; D010649:Phenylalanine / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism*; D014774:Virulence
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; D011991:Receptors, Virus; D010649:Phenylalanine
keywords: Hemagglutinin; Host range; Influenza virus; Pathogenicity; Receptor-binding affinity