title: Mechanism of fusion triggering by human parainfluenza virus type III: communication between viral glycoproteins during entry.
abstract: Parainfluenza viruses enter host cells by fusing the viral and target cell membranes via concerted action of their two envelope glycoproteins: the hemagglutinin-neuraminidase (HN) and the fusion protein (F). Receptor-bound HN triggers F to undergo conformational changes that render it fusion-competent. To address the role of receptor engagement and to elucidate how HN and F interact during the fusion process, we used bimolecular fluorescence complementation to follow the dynamics of human parainfluenza virus type 3 (HPIV3) HN/F pairs in living cells. We show that HN and F associate before receptor engagement. HN drives the formation of HN-F clusters at the site of fusion, and alterations in HN-F interaction determine the fusogenicity of the glycoprotein pair. An interactive site, at the HN dimer interface modulates HN fusion activation property, which is critical for infection of the natural host. This first evidence for the sequence of initial events that lead to viral entry may indicate a new paradigm for understanding Paramyxovirus infection.
authors: Departments of Pediatrics and of Microbiology and Immunology, Weill Medical College of Cornell University, New York, New York 10021.
authors: Matteo
authors: M
authors: Porotto
authors: Departments of Pediatrics and of Microbiology and Immunology, Weill Medical College of Cornell University, New York, New York 10021.
authors: Samantha G
authors: SG
authors: Palmer
authors: Departments of Pediatrics and of Microbiology and Immunology, Weill Medical College of Cornell University, New York, New York 10021.
authors: Laura M
authors: LM
authors: Palermo
authors: Departments of Pediatrics and of Microbiology and Immunology, Weill Medical College of Cornell University, New York, New York 10021. Electronic address: anm2047@med.cornell.edu.
authors: Anne
authors: A
authors: Moscona
mesh_terms: D057809:HEK293 Cells; D006389:Hemagglutinins, Viral / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D057054:Molecular Imaging; D009154:Mutation; D009439:Neuraminidase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010224:Parainfluenza Virus 3, Human / Q000378:metabolism / Q000502:physiology*; D011485:Protein Binding; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D011956:Receptors, Cell Surface / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D013379:Substrate Specificity; D014760:Viral Fusion Proteins / Q000378:metabolism*; D053586:Virus Internalization
chemical_list: D006389:Hemagglutinins, Viral; D011956:Receptors, Cell Surface; D014760:Viral Fusion Proteins; D009439:Neuraminidase