TY  - JOUR
A1  - Zapatero Belinchón, Francisco Jóse
A1  - Dietzel, Erik
A1  - Dolnik, Olga
A1  - Döhner, Katinka
A1  - Costa, Rui
A1  - Hertel, Barbara
A1  - Veselkova, Barbora
A1  - Kirui, Jared
A1  - Klintworth, Anneke
A1  - Manns, Michael P.
A1  - Pöhlmann, Stefan
A1  - Pietschmann, Thomas
A1  - Krey, Thomas
A1  - Ciesek, Sandra
A1  - Gerold, Gisa
A1  - Sodeik, Beate
A1  - Becker, Stephan
A1  - Hahn, Thomas von
T1  - Characterization of the filovirus-resistant cell line SH-SY5Y reveals redundant role of cell surface entry factors
T2  - Viruses
N2  - Filoviruses infect a wide range of cell types with the exception of lymphocytes. The intracellular proteins cathepsin B and L, two-pore channel 1 and 2, and bona fide receptor Niemann–Pick Disease C1 (NPC1) are essential for the endosomal phase of cell entry. However, earlier steps of filoviral infection remain poorly characterized. Numerous plasma membrane proteins have been implicated in attachment but it is still unclear which ones are sufficient for productive entry. To define a minimal set of host factors required for filoviral glycoprotein-driven cell entry, we screened twelve cell lines and identified the nonlymphocytic cell line SH-SY5Y to be specifically resistant to filovirus infection. Heterokaryons of SH-SY5Y cells fused to susceptible cells were susceptible to filoviruses, indicating that SH-SY5Y cells do not express a restriction factor but lack an enabling factor critical for filovirus entry. However, all tested cell lines expressed functional intracellular factors. Global gene expression profiling of known cell surface entry factors and protein expression levels of analyzed attachment factors did not reveal any correlation between susceptibility and expression of a specific host factor. Using binding assays with recombinant filovirus glycoprotein, we identified cell attachment as the step impaired in filovirus entry in SH-SY5Y cells. Individual overexpression of attachment factors T-cell immunoglobulin and mucin domain 1 (TIM-1), Axl, Mer, or dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) rendered SH-SY5Y cells susceptible to filovirus glycoprotein-driven transduction. Our study reveals that a lack of attachment factors limits filovirus entry and provides direct experimental support for a model of filoviral cell attachment where host factor usage at the cell surface is highly promiscuous.
KW  - Filovirus cell entry; attachment factors redundancy; SH-SY5Y cell line; host–pathogen interactions
Y1  - 2019
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/57199
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-571995
SN  - 1999-4915
VL  - 11
IS  - no. 3, art. 275
PB  - MDPI
CY  - Basel
ER  -