title: Full conversion of the hemagglutinin-neuraminidase specificity of the parainfluenza virus 5 fusion protein by replacement of 21 amino acids in its head region with those of the simian virus 41 fusion protein.
abstract: For most parainfluenza viruses, a virus type-specific interaction between the hemagglutinin-neuraminidase (HN) and fusion (F) proteins is a prerequisite for mediating virus-cell fusion and cell-cell fusion. The molecular basis of this functional interaction is still obscure partly because it is unknown which region of the F protein is responsible for the physical interaction with the HN protein. Our previous cell-cell fusion assay using the chimeric F proteins of parainfluenza virus 5 (PIV5) and simian virus 41 (SV41) indicated that replacement of two domains in the head region of the PIV5 F protein with the SV41 F counterparts bestowed on the PIV5 F protein the ability to induce cell-cell fusion on coexpression with the SV41 HN protein while retaining its ability to induce fusion with the PIV5 HN protein. In the study presented here, we furthered the chimeric analysis of the F proteins of PIV5 and SV41, finding that the PIV5 F protein could be converted to an SV41 HN-specific chimeric F protein by replacing five domains in the head region with the SV41 F counterparts. The five SV41 F-protein-derived domains of this chimera were then divided into 16 segments; 9 out of 16 proved to be not involved in determining its specificity for the SV41 HN protein. Finally, mutational analyses of a chimeric F protein, which harbored seven SV41 F-protein-derived segments, revealed that replacement of at most 21 amino acids of the PIV5 F protein with the SV41 F-protein counterparts was enough to convert its HN protein specificity.
authors.affiliation: Department of Microbiology and Molecular Genetics, Mie University Graduate School of Medicine, Tsu, Mie, Japan. turudome@doc.medic.mieu.ac.jp
authors.forename: Masato
authors.initials: M
authors.lastname: Tsurudome
authors.forename: Mito
authors.initials: M
authors.lastname: Nakahashi
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Matsushima
authors.forename: Morihiro
authors.initials: M
authors.lastname: Ito
authors.forename: Machiko
authors.initials: M
authors.lastname: Nishio
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Kawano
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Komada
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Nosaka
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002459:Cell Fusion; D002460:Cell Line; D006224:Cricetinae; D004252:DNA Mutational Analysis; D015707:HN Protein / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D011995:Recombination, Genetic; D019213:Rubulavirus / Q000235:genetics / Q000502:physiology*; D014760:Viral Fusion Proteins / Q000235:genetics / Q000378:metabolism*; D053586:Virus Internalization
chemical_list: D015707:HN Protein; D011993:Recombinant Fusion Proteins; D014760:Viral Fusion Proteins