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...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2012-11-01
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| Series: | Viruses |
| Subjects: | |
| Online Access: | http://www.mdpi.com/1999-4915/4/12/3336 |
| _version_ | 1811226215549239296 |
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| author | Stefan Pöhlmann Franziska Kaup Heike Hofmann-Winkler |
| author_facet | Stefan Pöhlmann Franziska Kaup Heike Hofmann-Winkler |
| author_sort | Stefan Pöhlmann |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-12T09:20:57Z |
| format | Article |
| id | doaj.art-e7af44df3e3e496c84487914bee6a910 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-04-12T09:20:57Z |
| publishDate | 2012-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-e7af44df3e3e496c84487914bee6a9102022-12-22T03:38:39ZengMDPI AGViruses1999-49152012-11-014123336336210.3390/v4123336Host Cell Factors in Filovirus Entry: Novel Players, New InsightsStefan PöhlmannFranziska KaupHeike Hofmann-WinklerFiloviruses 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.http://www.mdpi.com/1999-4915/4/12/3336filovirusEbolaMarburgentrycathepsinsTIM-1AxlNPC1 |
| spellingShingle | Stefan Pöhlmann Franziska Kaup Heike Hofmann-Winkler Host Cell Factors in Filovirus Entry: Novel Players, New Insights Viruses filovirus Ebola Marburg entry cathepsins TIM-1 Axl NPC1 |
| 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 amp 160 insights |
| topic | filovirus Ebola Marburg entry cathepsins TIM-1 Axl NPC1 |
| url | http://www.mdpi.com/1999-4915/4/12/3336 |
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