Interaction between the Hemagglutinin-Neuraminidase and Fusion Glycoproteins of Human Parainfluenza Virus Type III Regulates Viral Growth <italic toggle="yes">In Vivo</italic>

ABSTRACT Paramyxoviruses, enveloped RNA viruses that include human parainfluenza virus type 3 (HPIV3), cause the majority of childhood viral pneumonia. HPIV3 infection starts when the viral receptor-binding protein engages sialic acid receptors in the lung and the viral envelope fuses with the targe...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Rui Xu, Samantha G. Palmer, Matteo Porotto, Laura M. Palermo, Stefan Niewiesk, Ian A. Wilson, Anne Moscona
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2013
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/f9905693085245d6b7af8e16718b688e
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:f9905693085245d6b7af8e16718b688e
record_format	dspace
spelling	oai:doaj.org-article:f9905693085245d6b7af8e16718b688e2021-11-15T15:42:47ZInteraction between the Hemagglutinin-Neuraminidase and Fusion Glycoproteins of Human Parainfluenza Virus Type III Regulates Viral Growth <italic toggle="yes">In Vivo</italic>10.1128/mBio.00803-132150-7511https://doaj.org/article/f9905693085245d6b7af8e16718b688e2013-11-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00803-13https://doaj.org/toc/2150-7511ABSTRACT Paramyxoviruses, enveloped RNA viruses that include human parainfluenza virus type 3 (HPIV3), cause the majority of childhood viral pneumonia. HPIV3 infection starts when the viral receptor-binding protein engages sialic acid receptors in the lung and the viral envelope fuses with the target cell membrane. Fusion/entry requires interaction between two viral surface glycoproteins: tetrameric hemagglutinin-neuraminidase (HN) and fusion protein (F). In this report, we define structural correlates of the HN features that permit infection in vivo. We have shown that viruses with an HN-F that promotes growth in cultured immortalized cells are impaired in differentiated human airway epithelial cell cultures (HAE) and in vivo and evolve in HAE into viable viruses with less fusogenic HN-F. In this report, we identify specific structural features of the HN dimer interface that modulate HN-F interaction and fusion triggering and directly impact infection. Crystal structures of HN, which promotes viral growth in vivo, show a diminished interface in the HN dimer compared to the reference strain’s HN, consistent with biochemical and biological data indicating decreased dimerization and decreased interaction with F protein. The crystallographic data suggest a structural explanation for the HN’s altered ability to activate F and reveal properties that are critical for infection in vivo. IMPORTANCE Human parainfluenza viruses cause the majority of childhood cases of croup, bronchiolitis, and pneumonia worldwide. Enveloped viruses must fuse their membranes with the target cell membranes in order to initiate infection. Parainfluenza fusion proceeds via a multistep reaction orchestrated by the two glycoproteins that make up its fusion machine. In vivo, viruses adapt for survival by evolving to acquire a set of fusion machinery features that provide key clues about requirements for infection in human beings. Infection of the lung by parainfluenzavirus is determined by specific interactions between the receptor binding molecule (hemagglutinin-neuraminidase [HN]) and the fusion protein (F). Here we identify specific structural features of the HN dimer interface that modulate HN-F interaction and fusion and directly impact infection. The crystallographic and biochemical data point to a structural explanation for the HN’s altered ability to activate F for fusion and reveal properties that are critical for infection by this important lung virus in vivo.Rui XuSamantha G. PalmerMatteo PorottoLaura M. PalermoStefan NiewieskIan A. WilsonAnne MosconaAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 4, Iss 5 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Rui Xu Samantha G. Palmer Matteo Porotto Laura M. Palermo Stefan Niewiesk Ian A. Wilson Anne Moscona Interaction between the Hemagglutinin-Neuraminidase and Fusion Glycoproteins of Human Parainfluenza Virus Type III Regulates Viral Growth <italic toggle="yes">In Vivo</italic>
description	ABSTRACT Paramyxoviruses, enveloped RNA viruses that include human parainfluenza virus type 3 (HPIV3), cause the majority of childhood viral pneumonia. HPIV3 infection starts when the viral receptor-binding protein engages sialic acid receptors in the lung and the viral envelope fuses with the target cell membrane. Fusion/entry requires interaction between two viral surface glycoproteins: tetrameric hemagglutinin-neuraminidase (HN) and fusion protein (F). In this report, we define structural correlates of the HN features that permit infection in vivo. We have shown that viruses with an HN-F that promotes growth in cultured immortalized cells are impaired in differentiated human airway epithelial cell cultures (HAE) and in vivo and evolve in HAE into viable viruses with less fusogenic HN-F. In this report, we identify specific structural features of the HN dimer interface that modulate HN-F interaction and fusion triggering and directly impact infection. Crystal structures of HN, which promotes viral growth in vivo, show a diminished interface in the HN dimer compared to the reference strain’s HN, consistent with biochemical and biological data indicating decreased dimerization and decreased interaction with F protein. The crystallographic data suggest a structural explanation for the HN’s altered ability to activate F and reveal properties that are critical for infection in vivo. IMPORTANCE Human parainfluenza viruses cause the majority of childhood cases of croup, bronchiolitis, and pneumonia worldwide. Enveloped viruses must fuse their membranes with the target cell membranes in order to initiate infection. Parainfluenza fusion proceeds via a multistep reaction orchestrated by the two glycoproteins that make up its fusion machine. In vivo, viruses adapt for survival by evolving to acquire a set of fusion machinery features that provide key clues about requirements for infection in human beings. Infection of the lung by parainfluenzavirus is determined by specific interactions between the receptor binding molecule (hemagglutinin-neuraminidase [HN]) and the fusion protein (F). Here we identify specific structural features of the HN dimer interface that modulate HN-F interaction and fusion and directly impact infection. The crystallographic and biochemical data point to a structural explanation for the HN’s altered ability to activate F for fusion and reveal properties that are critical for infection by this important lung virus in vivo.
format	article
author	Rui Xu Samantha G. Palmer Matteo Porotto Laura M. Palermo Stefan Niewiesk Ian A. Wilson Anne Moscona
author_facet	Rui Xu Samantha G. Palmer Matteo Porotto Laura M. Palermo Stefan Niewiesk Ian A. Wilson Anne Moscona
author_sort	Rui Xu
title	Interaction between the Hemagglutinin-Neuraminidase and Fusion Glycoproteins of Human Parainfluenza Virus Type III Regulates Viral Growth <italic toggle="yes">In Vivo</italic>
title_short	Interaction between the Hemagglutinin-Neuraminidase and Fusion Glycoproteins of Human Parainfluenza Virus Type III Regulates Viral Growth <italic toggle="yes">In Vivo</italic>
title_full	Interaction between the Hemagglutinin-Neuraminidase and Fusion Glycoproteins of Human Parainfluenza Virus Type III Regulates Viral Growth <italic toggle="yes">In Vivo</italic>
title_fullStr	Interaction between the Hemagglutinin-Neuraminidase and Fusion Glycoproteins of Human Parainfluenza Virus Type III Regulates Viral Growth <italic toggle="yes">In Vivo</italic>
title_full_unstemmed	Interaction between the Hemagglutinin-Neuraminidase and Fusion Glycoproteins of Human Parainfluenza Virus Type III Regulates Viral Growth <italic toggle="yes">In Vivo</italic>
title_sort	interaction between the hemagglutinin-neuraminidase and fusion glycoproteins of human parainfluenza virus type iii regulates viral growth <italic toggle="yes">in vivo</italic>
publisher	American Society for Microbiology
publishDate	2013
url	https://doaj.org/article/f9905693085245d6b7af8e16718b688e
work_keys_str_mv	AT ruixu interactionbetweenthehemagglutininneuraminidaseandfusionglycoproteinsofhumanparainfluenzavirustypeiiiregulatesviralgrowthitalictoggleyesinvivoitalic AT samanthagpalmer interactionbetweenthehemagglutininneuraminidaseandfusionglycoproteinsofhumanparainfluenzavirustypeiiiregulatesviralgrowthitalictoggleyesinvivoitalic AT matteoporotto interactionbetweenthehemagglutininneuraminidaseandfusionglycoproteinsofhumanparainfluenzavirustypeiiiregulatesviralgrowthitalictoggleyesinvivoitalic AT laurampalermo interactionbetweenthehemagglutininneuraminidaseandfusionglycoproteinsofhumanparainfluenzavirustypeiiiregulatesviralgrowthitalictoggleyesinvivoitalic AT stefanniewiesk interactionbetweenthehemagglutininneuraminidaseandfusionglycoproteinsofhumanparainfluenzavirustypeiiiregulatesviralgrowthitalictoggleyesinvivoitalic AT ianawilson interactionbetweenthehemagglutininneuraminidaseandfusionglycoproteinsofhumanparainfluenzavirustypeiiiregulatesviralgrowthitalictoggleyesinvivoitalic AT annemoscona interactionbetweenthehemagglutininneuraminidaseandfusionglycoproteinsofhumanparainfluenzavirustypeiiiregulatesviralgrowthitalictoggleyesinvivoitalic
_version_	1718427621043208192

Interaction between the Hemagglutinin-Neuraminidase and Fusion Glycoproteins of Human Parainfluenza Virus Type III Regulates Viral Growth <italic toggle="yes">In Vivo</italic>

Ejemplares similares