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

German Primate Center, Infection Biology Unit, Kellnerweg 4, 37077 Göttingen, Germany
Authors to whom correspondence should be addressed.
Viruses 2012, 4(12), 3336-3362;
Received: 23 October 2012 / Revised: 12 November 2012 / Accepted: 13 November 2012 / Published: 26 November 2012
(This article belongs to the Special Issue Advances in Filovirus Research 2012)
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. View Full-Text
Keywords: filovirus; Ebola; Marburg; entry; cathepsins; TIM-1; Axl; NPC1 filovirus; Ebola; Marburg; entry; cathepsins; TIM-1; Axl; NPC1
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Hofmann-Winkler, H.; Kaup, F.; Pöhlmann, S. Host Cell Factors in Filovirus Entry: Novel Players, New Insights. Viruses 2012, 4, 3336-3362.

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