The study of human respiratory syncytial virus (RSV) A entry into HeLa and A549 cells using fluorescence microscopy and quantitative FACS assays has shown that, after attachment, RSV rapidly enters host cells by an actin-dependent process with characteristics of macropinocytosis. Findings are similar when primary bronchial epithelial cells are used (Krzyzaniak et al. 2013). Macropinocytosis requires activation of receptor tyrosine kinases (RTKs). The only RTK activated in experiments with HeLa and A549 cells is EGFR, and EGFR inhibitors block RSV entry (Krzyzaniak et al. 2013). EGFR has been reported to interact with the F protein of some RSV strains (Currier et al. 2016). However, in the airway epithelium, EGFR is mainly expressed in basal cells while the RTK IGF1R has been shown to be the binding partner for the F protein in the hRSV A2 strain and is required for RSV entry into ciliated epithelial cells of the airways (Griffiths et al. 2020). Protein kinase C signaling appears to be important for macropinocytosis-mediated entry of RSV (Krzyzaniak et al. 2013). Protein kinase C zeta (PRKCZ) has been shown to be activated downstream of IGF1R and seems to be important for RSV entry as it increases the concentration of the F protein binding partner, NCL, at the surface of ciliated airway epithelium (Griffiths et al. 2020). NCL has been reported to be involved in promotion of macropinocytosis (Reyes-Reyes et al. 2010; Reyes-Reyes et al. 2015). Other host cell factors implicated in RSV macropinocytosis are PI3K, RAC1 and CDC42 GTPases, PAK1 kinase - downstream effector of RAC1 and CDC42, myosin II - PAK1 target, Na+/H+ exchangers, and RAB5 macropinosome marker (Krzyzaniak et al. 2013).