Filovirus entry into susceptible cells

Filoviruses cause highly lethal zoonotic infections in humans and nonhuman primates. The filamentous nucleocapsid core of filovirus virions is enveloped by a host-derived lipid bilayer, in which are embedded trimers of the viral glycoprotein (GP). GP is both sufficient and necessary for filovirus entry into susceptible target cells. Intense research in the last couple of decades has greatly increased our understanding of how these viruses exploit cellular pathways to enter cells and initiate infection. Virions are taken up by a macropinocytosislike process and trafficked to endo/lysosomes where endosomal cysteine proteases prime the viral GP to bind to the essential endosomal receptor, Niemann-Pick C1 (NPC1). After engaging NPC1, viral GP is proposed to undergo extensive conformational changes that lead to fusion of the viral envelope with a cellular membrane, thereby releasing the viral genome into the cytoplasm. This chapter reviews our current understanding of the filovirus entry mechanism, while emphasizing important unanswered questions in the field.