Figure 3.

Working Model on the Different Consequences of Cell Entry upon Membrane-Distal Attachment of Receptor-Targeted NiV-LVs and MV-LVs

(A) MV-LV membrane fusion is independent of the distance of the targeting ligand’s binding site at the entry receptor from the host cell membrane. Because of the low glycoprotein density on the vector particle surface, MV-LVs bind to only a few target receptors. This leaves them more flexibility for positioning at the optimal distance to the cell surface that is required for the fusion peptide to become inserted into the cell membrane. Thus, gene delivery by MV-LVs is less influenced by the relative distance of the binding site on the target receptor from the membrane. (B) In contrast, NiV-LVs require target receptor binding close to the cell membrane for productive fusion. Due to the high glycoprotein density on the particle surface, NiV-LVs make multiple receptor contacts, which results in a rigid position of the particle-target receptor complex and a fixed distance from the target cell membrane. If this distance exceeds 210 Å, which is the distance covered by fusion-active F protein,⁶⁶ insertion of the fusion peptide of the F protein into the cell membrane and subsequent fusion cannot take place.