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Seminario: Enhanced cell-binding and infectivity through DC-SIGN in the West African Ebola virus
Miércoles, 22. Mayo 2019, 12:00
Contacto Jose Miguel Mancheño Gómez

Since its discovery in Zaire in 1976, most ebolavirus outbreaks described occurred mainly in remote and poorly communicated areas of Central Africa and affected a limited number of individuals.

Since its discovery in Zaire in 1976, most ebolavirus outbreaks described occurred mainly in remote and poorly communicated areas of Central Africa and affected a limited number of individuals. Nonetheless, the Ebola epidemic that began in West Africa at the end of 2013 spread rapidly and reached an unprecedented scale. This epidemic was caused by the Makona variant of Zaire ebolavirus (EBOV). Monitoring of the EBOV Makona evolution throughout the epidemic identified the A82V substitution in the EBOV glycoprotein (GP) at the beginning of the epidemic, which correlated with its rapid spread. The Makona GP-V82 variant exhibits slightly higher human and primate cell infectivity. Host factors responsible for the enhanced transmission of EBOV Makona have yet to be identified. We now show that the GP A82V substitution increases EBOV avidity for its DC-SIGN lectin receptor, which enhances cell-binding and infectivity of dendritic cells and macrophages, the primary cell subsets infected during the initial stages of the disease. Using a pseudotype lentivirus system, we identified two GP N-linked glycosylation responsible of the augmented Makona GP-V82 cell infection. Crystal structures indicate how the GP A82V substitution drives exposure of a key glycan and facilitates lectin recognition. Thus, DC-SIGN might be an important host determinant for the unique dissemination of EBOV during the 2013-2016 epidemic, which likely promoted host-to-host transmission by enhancing viral infection of dendritic cells in the skin and mucosa. This study also reveals that variations in virus envelope glycosylations can be a common pathway for virus adaptation to human transmission.

Fecha del seminario: 22/05/2019 12:00

Lugar del seminario: Salón de Actos del Instituto Rocasolano.

Ponente del seminario: Rafael Delgado

Abstract

Localización Salón de actos del IQFR

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Proyectos financiados por

ERC