FIGURE 3: The current models for the role of NPC1 in replication of infectious viruses such as EBOV and HIV-1. Infectious haemorrhagic fever (A-B). EBOV is transported to lysosomes at which point the virally encoded glycoprotein (GP) interacts with NPC1 to release nucleocapsid for replication and cytoplasmic release via lipid rafts [138]. In NPC1 deficient states, the cytoplasmic release of EBOV is disrupted without efficient replication of EBOV. Acquired Immunodeficiency Syndrome (C-D). Free cholesterol egressed from the lysosome by NPC1 or NPC2 is a subset of the cholesterol pool utilized by HIV-1 for replication [143]. Mutations in NPC1 reduce cholesterol availability and increase GAG protein accumulation, thereby impeding the cytoplasmic release and replication of HIV-1 virions.

138. Carette JE, Raaben M, Wong AC, Herbert AS, Obernosterer G, Mulherkar N, Kuehne AI, Kranzusch PJ, Griffin AM, Ruthel G, Dal Cin P, Dye JM, Whelan SP, Chandran K, and Brummelkamp TR (2011). Ebola virus entry requires the cholesterol transporter Niemann-Pick C1. Nature 477(7364): 340–343. https://doi.org/10.1038/nature10348

143. Zheng Y-H, Plemenitas A, Fielding CJ, and Peterlin BM (2003). Nef increases the synthesis of and transports cholesterol to lipid rafts and HIV-1 progeny virions. Proc Natl Acad Sci USA 100(14): 8460–8465. https://doi.org/10.1073/pnas.1437453100