Similar to endosomes, macropinosomes gradually acidify, acquiring RAB5 followed by RAB7 before fusing with endolysosomes. Human respiratory syncytial virus (RSV) A co-localizes with RAB5-positive macropinosomes and depends on the GTPase activity of RAB5 for infection of host cells, but not on the activity of RAB7. Co-localization of RSV with RAB7 was only observed when RAB5 was defective, and full maturation of macropinosomes was not required for RSV infection, indicating that the RSV membrane fuses with the macropinosome membrane during maturation of RAB5-positive macropinosomes, releasing the ribonucleocapsid (RNP) into the cytosol of the host cell (Krzyzaniak et al. 2013). RAB5C was independently shown to be important for RSV infection (Li et al. 2020), supporting the involvement of RAB5-positive macropinosomes. The release of RSV from RAB5-positive macropinosomes requires the activity of FURIN-like convertase that cleaves the mature F protein (F1-F2 peptide), releasing a glycosylated peptide of 27 amino acids (p27) to allow the fusion of the viral membrane with the macropinosomes membrane (Krzyzaniak et al. 2013). FURIN-mediated cleavage of F1-F2 mature form of F protein with the release of glycosylated p27 fragment was previously reported to be needed for RSV-mediated syncytia formation (Zimmer et al. 2001)