title: Type II integral membrane protein, TM of J paramyxovirus promotes cell-to-cell fusion.
abstract: Paramyxoviruses include many important animal and human pathogens. Most paramyxoviruses have two integral membrane proteins: fusion protein (F) and attachment proteins hemagglutinin, hemagglutinin-neuraminidase, or glycoprotein (G), which are critical for viral entry into cells. J paramyxovirus (JPV) encodes four integral membrane proteins: F, G, SH, and transmembrane (TM). The function of TM is not known. In this work, we have generated a viable JPV lacking TM (JPV∆TM). JPV∆TM formed opaque plaques compared with JPV. Quantitative syncytia assays showed that JPV∆TM was defective in promoting cell-to-cell fusion (i.e., syncytia formation) compared with JPV. Furthermore, cells separately expressing F, G, TM, or F plus G did not form syncytia whereas cells expressing F plus TM formed some syncytia. However, syncytia formation was much greater with coexpression of F, G, and TM. Biochemical analysis indicates that F, G, and TM interact with each other. A small hydrophobic region in the TM ectodomain from amino acid residues 118 to 132, the hydrophobic loop (HL), was important for syncytial promotion, suggesting that the TM HL region plays a critical role in cell-to-cell fusion.
authors.affiliation: Department of Infectious Disease, College of Veterinary Medicine, University of Georgia, Athens, GA 30602;
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Infectious Disease, College of Veterinary Medicine, University of Georgia, Athens, GA 30602;
authors.forename: Cher
authors.initials: C
authors.lastname: Hung
authors.affiliation: Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208-3500;
authors.forename: Reay G
authors.initials: RG
authors.lastname: Paterson
authors.affiliation: Department of Infectious Disease, College of Veterinary Medicine, University of Georgia, Athens, GA 30602;
authors.forename: Frank
authors.initials: F
authors.lastname: Michel
authors.affiliation: Department of Infectious Disease, College of Veterinary Medicine, University of Georgia, Athens, GA 30602;
authors.forename: Sandra
authors.initials: S
authors.lastname: Fuentes
authors.affiliation: Department of Infectious Disease, College of Veterinary Medicine, University of Georgia, Athens, GA 30602;
authors.forename: Ryan
authors.initials: R
authors.lastname: Place
authors.affiliation: Department of Infectious Disease, College of Veterinary Medicine, University of Georgia, Athens, GA 30602;
authors.forename: Yuan
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Department of Infectious Disease, College of Veterinary Medicine, University of Georgia, Athens, GA 30602;
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Hogan
authors.affiliation: Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208-3500; Howard Hughes Medical Institute, Northwestern University, Evanston, IL 60208-3500.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Lamb
authors.affiliation: Department of Infectious Disease, College of Veterinary Medicine, University of Georgia, Athens, GA 30602; bhe@uga.edu.
authors.forename: Biao
authors.initials: B
authors.lastname: He
mesh_terms: D000818:Animals; D002459:Cell Fusion; D002460:Cell Line; D002522:Chlorocebus aethiops; D004591:Electrophoresis, Polyacrylamide Gel; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D015726:Giant Cells / Q000378:metabolism; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D018098:Paramyxovirinae / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D011485:Protein Binding; D014709:Vero Cells; D014760:Viral Fusion Proteins / Q000235:genetics / Q000378:metabolism; D010948:Viral Plaque Assay; D014764:Viral Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D006023:Glycoproteins; D008565:Membrane Proteins; D014760:Viral Fusion Proteins; D014764:Viral Proteins
keywords: J paramyxovirus; TM; fusion; syncytia