Filovirus Entry: A Novelty in the Viral Fusion World

Hunt, Catherine L.; Lennemann, Nicholas J.; Maury, Wendy

As the NPC1 protein is primarily located on the endosomal and lysosomal membranes, NPC1 has been proposed to serve as an entry factor downstream of EBOV GP engagement of attachment factors/receptor(s) at the cell surface. Consistent with a vesicular role for NPC1, Cote et al. showed that a soluble form of thermolysin-cleaved EBOV GP, but not uncleaved GP containing the glycan cap, bound to lysosomal membranes of NPC1-transfected CHO cells [83] . Thus, at least in this over expression system, proteolytically-processed EBOV GP appeared to interact with NPC1-containing membranes, suggesting that these interactions may be important for filovirus entry events that occur in late endosomes and/or in lysosomes. EBOV GP-mediated attachment and entry into early endosomes was unaffected in NPC1-defective cells; however, electron micrographs of NPC1 null cells infected with EBOV GP pseudotyped virus show the accumulation of perinuclear vesicles laden with EBOV GP pseudovirions that were positive for the lysosomal marker LAMP1 [84] . Therefore, Carette et al. have proposed that NCP1 is crucial for viral membrane fusion and escape from the lysosomal vesicle [84] . At present, the precise role of NPC1 during the EBOV entry process remains to be fully elucidated. In addition, investigations into the precise location of filovirus fusion events within endosomal compartments will provide important insights into these events.