Cargando…

Influenza A virus surface proteins are organized to help penetrate host mucus

Influenza A virus (IAV) enters cells by binding to sialic acid on the cell surface. To accomplish this while avoiding immobilization by sialic acid in host mucus, viruses rely on a balance between the receptor-binding protein hemagglutinin (HA) and the receptor-cleaving protein neuraminidase (NA). A...

Descripción completa

Detalles Bibliográficos
Autores principales: Vahey, Michael D, Fletcher, Daniel A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6516830/
https://www.ncbi.nlm.nih.gov/pubmed/31084711
http://dx.doi.org/10.7554/eLife.43764
_version_ 1783418242343108608
author Vahey, Michael D
Fletcher, Daniel A
author_facet Vahey, Michael D
Fletcher, Daniel A
author_sort Vahey, Michael D
collection PubMed
description Influenza A virus (IAV) enters cells by binding to sialic acid on the cell surface. To accomplish this while avoiding immobilization by sialic acid in host mucus, viruses rely on a balance between the receptor-binding protein hemagglutinin (HA) and the receptor-cleaving protein neuraminidase (NA). Although genetic aspects of this balance are well-characterized, little is known about how the spatial organization of these proteins in the viral envelope may contribute. Using site-specific fluorescent labeling and super-resolution microscopy, we show that HA and NA are asymmetrically distributed on the surface of filamentous viruses, creating a spatial organization of binding and cleaving activities that causes viruses to step consistently away from their NA-rich pole. This Brownian ratchet-like diffusion produces persistent directional mobility that resolves the virus’s conflicting needs to both penetrate mucus and stably attach to the underlying cells, potentially contributing to the prevalence of the filamentous phenotype in clinical isolates of IAV.
format Online
Article
Text
id pubmed-6516830
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher eLife Sciences Publications, Ltd
record_format MEDLINE/PubMed
spelling pubmed-65168302019-05-16 Influenza A virus surface proteins are organized to help penetrate host mucus Vahey, Michael D Fletcher, Daniel A eLife Microbiology and Infectious Disease Influenza A virus (IAV) enters cells by binding to sialic acid on the cell surface. To accomplish this while avoiding immobilization by sialic acid in host mucus, viruses rely on a balance between the receptor-binding protein hemagglutinin (HA) and the receptor-cleaving protein neuraminidase (NA). Although genetic aspects of this balance are well-characterized, little is known about how the spatial organization of these proteins in the viral envelope may contribute. Using site-specific fluorescent labeling and super-resolution microscopy, we show that HA and NA are asymmetrically distributed on the surface of filamentous viruses, creating a spatial organization of binding and cleaving activities that causes viruses to step consistently away from their NA-rich pole. This Brownian ratchet-like diffusion produces persistent directional mobility that resolves the virus’s conflicting needs to both penetrate mucus and stably attach to the underlying cells, potentially contributing to the prevalence of the filamentous phenotype in clinical isolates of IAV. eLife Sciences Publications, Ltd 2019-05-14 /pmc/articles/PMC6516830/ /pubmed/31084711 http://dx.doi.org/10.7554/eLife.43764 Text en © 2019, Vahey and Fletcher http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Microbiology and Infectious Disease
Vahey, Michael D
Fletcher, Daniel A
Influenza A virus surface proteins are organized to help penetrate host mucus
title Influenza A virus surface proteins are organized to help penetrate host mucus
title_full Influenza A virus surface proteins are organized to help penetrate host mucus
title_fullStr Influenza A virus surface proteins are organized to help penetrate host mucus
title_full_unstemmed Influenza A virus surface proteins are organized to help penetrate host mucus
title_short Influenza A virus surface proteins are organized to help penetrate host mucus
title_sort influenza a virus surface proteins are organized to help penetrate host mucus
topic Microbiology and Infectious Disease
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6516830/
https://www.ncbi.nlm.nih.gov/pubmed/31084711
http://dx.doi.org/10.7554/eLife.43764
work_keys_str_mv AT vaheymichaeld influenzaavirussurfaceproteinsareorganizedtohelppenetratehostmucus
AT fletcherdaniela influenzaavirussurfaceproteinsareorganizedtohelppenetratehostmucus