Filovirus entry into cells – new insights

Filoviruses are hemorrhagic fever-causing agents that produce enveloped virions with a filamentous morphology. The viral surface glycoprotein, GP, orchestrates the surprisingly complex process by which filoviruses gain access to the cytoplasm of their host cells. GP mediates viral attachment to cells through multiple, redundant interactions with cell-surface factors. GP then induces virion internalization by a process that resembles cellular macropinocytosis. Within the endo/lysosomal pathway, GP undergoes a series of structural rearrangements, controlled by interactions with host factors, that prime and activate it to bring about fusion between the viral and cellular lipid bilayers. Membrane fusion delivers the viral nucleocapsid core into the cytoplasm, which is the site of filovirus replication. This review summarizes our understanding of the filovirus entry mechanism, with emphasis on recent findings.

► The filovirus glycoprotein, GP, mediates viral entry into the host cell cytoplasm. ► Multiple cell surface molecules play roles in filovirus attachment to cells. ► Unknown GP–host cell interactions induce viral internalization into endosomes via a pathway resembling macropinocytosis. ► Niemann-Pick C1, an endo/lysosomal cholesterol transport protein, is a critical host factor for filovirus entry that may interact with a cleaved form of GP. ► The host trigger for filovirus membrane fusion is unknown, and structural intermediates in the fusion reaction are poorly characterized.