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Host Cell Factors in Filovirus Entry: Novel Players, New Insights

Filoviruses cause severe hemorrhagic fever in humans with high case-fatality rates. The cellular factors exploited by filoviruses for their spread constitute potential targets for intervention, but are incompletely defined. The viral glycoprotein (GP) mediates filovirus entry into host cells. Recent...

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Autores principales: Hofmann-Winkler, Heike, Kaup, Franziska, Pöhlmann, Stefan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3528269/
https://www.ncbi.nlm.nih.gov/pubmed/23342362
http://dx.doi.org/10.3390/v4123336
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author Hofmann-Winkler, Heike
Kaup, Franziska
Pöhlmann, Stefan
author_facet Hofmann-Winkler, Heike
Kaup, Franziska
Pöhlmann, Stefan
author_sort Hofmann-Winkler, Heike
collection PubMed
description Filoviruses cause severe hemorrhagic fever in humans with high case-fatality rates. The cellular factors exploited by filoviruses for their spread constitute potential targets for intervention, but are incompletely defined. The viral glycoprotein (GP) mediates filovirus entry into host cells. Recent studies revealed important insights into the host cell molecules engaged by GP for cellular entry. The binding of GP to cellular lectins was found to concentrate virions onto susceptible cells and might contribute to the early and sustained infection of macrophages and dendritic cells, important viral targets. Tyrosine kinase receptors were shown to promote macropinocytic uptake of filoviruses into a subset of susceptible cells without binding to GP, while interactions between GP and human T cell Ig mucin 1 (TIM-1) might contribute to filovirus infection of mucosal epithelial cells. Moreover, GP engagement of the cholesterol transporter Niemann-Pick C1 was demonstrated to be essential for GP-mediated fusion of the viral envelope with a host cell membrane. Finally, mutagenic and structural analyses defined GP domains which interact with these host cell factors. Here, we will review the recent progress in elucidating the molecular interactions underlying filovirus entry and discuss their implications for our understanding of the viral cell tropism.
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spelling pubmed-35282692013-01-02 Host Cell Factors in Filovirus Entry: Novel Players, New Insights Hofmann-Winkler, Heike Kaup, Franziska Pöhlmann, Stefan Viruses Review Filoviruses cause severe hemorrhagic fever in humans with high case-fatality rates. The cellular factors exploited by filoviruses for their spread constitute potential targets for intervention, but are incompletely defined. The viral glycoprotein (GP) mediates filovirus entry into host cells. Recent studies revealed important insights into the host cell molecules engaged by GP for cellular entry. The binding of GP to cellular lectins was found to concentrate virions onto susceptible cells and might contribute to the early and sustained infection of macrophages and dendritic cells, important viral targets. Tyrosine kinase receptors were shown to promote macropinocytic uptake of filoviruses into a subset of susceptible cells without binding to GP, while interactions between GP and human T cell Ig mucin 1 (TIM-1) might contribute to filovirus infection of mucosal epithelial cells. Moreover, GP engagement of the cholesterol transporter Niemann-Pick C1 was demonstrated to be essential for GP-mediated fusion of the viral envelope with a host cell membrane. Finally, mutagenic and structural analyses defined GP domains which interact with these host cell factors. Here, we will review the recent progress in elucidating the molecular interactions underlying filovirus entry and discuss their implications for our understanding of the viral cell tropism. MDPI 2012-11-26 /pmc/articles/PMC3528269/ /pubmed/23342362 http://dx.doi.org/10.3390/v4123336 Text en © 2012 by the authors; licensee MDPI, Basel, Switzerland. http://creativecommons.org/licenses/by/3.0/ This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Review
Hofmann-Winkler, Heike
Kaup, Franziska
Pöhlmann, Stefan
Host Cell Factors in Filovirus Entry: Novel Players, New Insights
title Host Cell Factors in Filovirus Entry: Novel Players, New Insights
title_full Host Cell Factors in Filovirus Entry: Novel Players, New Insights
title_fullStr Host Cell Factors in Filovirus Entry: Novel Players, New Insights
title_full_unstemmed Host Cell Factors in Filovirus Entry: Novel Players, New Insights
title_short Host Cell Factors in Filovirus Entry: Novel Players, New Insights
title_sort host cell factors in filovirus entry: novel players, new insights
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3528269/
https://www.ncbi.nlm.nih.gov/pubmed/23342362
http://dx.doi.org/10.3390/v4123336
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