Figure 1.

Examples of viral entry pathways. (a) HIV-1 initially binds to the cell via interactions of the receptor-binding subunit gp120 of the viral GP Env with the receptor CD4 on the plasma membrane surface. This interaction induces a conformational change in gp120 that exposes a second receptor-binding domain. Interaction of this site with the coreceptor, CCR5 or CXCR4, triggers structural changes within the fusogenic subunit gp41 that are coupled to fusion of the viral and plasma membranes. (b) Influenza virus initially attaches to sialic acid on the cell surface and is then internalized by clathrin-dependent endocytosis. The reduced pH of the late endosome is the physiological trigger for the structural changes in hemagglutinin leading to fusion of the viral and endosomal membranes. (c) Ebola virus attaches to the host plasma membrane through interaction with surface factors, such as DC-SIGN and TIM-1, and then is internalized by macropinocytosis. The viral GP is proteolytically cleaved by cathepsins B or L in the endosome to form GP1 and GP2. The acidic environment of the late endosome further facilitates the interaction of GP1 with the internal receptor NPC1, which is believed to be the trigger for changes in GP2 structure that are coupled with fusion of the viral and endosomal membranes. Abbreviations: DC-SIGN, dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin; GP, glycoprotein; HIV-1, human immunodeficiency virus type 1; NPC1, Niemann-Pick type C1; TIM-1, T cell immunoglobulin and mucin domain 1. Figure adapted from images created with BioRender.com.