lvarez CP, Carrillo J, Lasala F, Muniz O, Corbi AL, Delgado R; International Conference on AIDS.
Int Conf AIDS. 2002 Jul 7-12; 14: abstract no. TuPeA4358.
Hospital 12 de Octubre, Madrid, Spain
BACKGROUND: Ebola Virus (EV) is a highly lethal pathogen responsible for several outbreaks of hemorrhagic fever. The cellular factors implicated in Ebola Virus cell entry remain largely unknown. DC-SIGN and its homologue L-SIGN have been shown to bind most lentiviruses of primates: HIV-1, HIV-2 and SIV, although they do not act as receptors for cellular entry. The affinity of these membrane receptors for retroviral glycoproteins and their tissue distribution pattern prompted us to study their potential role as binding and entry co-factors for EV. METHODS: Recombinant luciferase-expressing lentiviral particles pseudotyped with the EV envelope glycoprotein (Ebo-GP) were used for binding and infection experiments. DC or L-SIGN expression on different cell lines was achieved by transient and stable transfection and by retroviral transduction in the non-permissive Jurkat cell line. The physiological role of Ebo-GP and lectin interaction was explored by using Monocyte-derived Dendritic cells (MDDC). RESULTS: DC-SIGN and L-SIGN-mediated EV infection was shown in different experimental approaches using transient and stable transfected cell lines. We demonstrate that expression of DC-SIGN or L-SIGN in the non-permissive Jurkat cell line is sufficient to confer susceptibility to EV infection. The physiological role of these molecules in EV infection was further emphasized by showing that DC-SIGN on the surface of MDDC is able to function as a trans-receptor, binding Ebo-GP pseudotyped lentiviral particles and transmitting infection to susceptible cells. CONCLUSIONS: Here we show that DC-SIGN and L-SIGN act as cofactors for cellular entry by Ebola Virus both in cis and in trans. Our data underscore a critical role for DC-SIGN and L-SIGN in the infective process and pathogenicity of Ebola Virus Infection and suggest an extended participation of these molecules in other viral infections.
Publication Types:
Keywords:
- Cell Adhesion Molecules
- Cell Line
- DC-specific ICAM-3 grabbing nonintegrin
- Dendritic Cells
- Ebolavirus
- Glycoproteins
- HIV-1
- Lectins
- Lectins, C-Type
- Lentivirus
- Monocytes
- Receptors, Cell Surface
- Rhabdoviridae
- Simian immunodeficiency virus
- cerebellar soluble lectin
- immunology
Other ID:
UI: 102254192
From Meeting Abstracts