Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infections in young children, elderly and immunocompromised patients worldwide. The RSV fusion (F) protein, which has 5–6 N-glycosylation sites depending on the strain, is a major target for vaccine development. Two to three of these sites are located in the p27 peptide, which is considered absent in virions. Prior research from our group showed that removing the N-glycan at position 116 (N116) in p27 led to higher neutralizing antibody responses and better protection against RSV. In this study, the effect of single, double and triple N-glycan deletion mutations in F p27 was evaluated. Surprisingly, all mutants exhibited similar expressions and functionality to the wild-type F protein. All F p27 glycomutants induced neutralizing antibodies and lowered lung viral loads after an RSV challenge in a mouse model. Although N-glycans in p27 influence immune responses, their exact role in RSV biology remains unclear. Possibly, these glycans, which are mostly conserved, play a role in other aspects of virus replication and biology.

Respiratory syncytial virus (RSV) is a major cause of severe respiratory infections in infants, the elderly, and immunocompromised persons. Innate immune responses to RSV, which are crucial for containment of the infection yet may also be linked to severe disease, are well-studied in the main RSV target cells, respiratory epithelial cells, but the role of pulmonary macrophages (MΦs), key innate immune regulators, remains incompletely defined. This review addresses the interaction of RSV with MΦ, discussing the susceptibility of these cells to productive infection, and MΦ responses to RSV, including cytokine and chemokine release and inflammasome activation. Furthermore, factors contributing to variability in MΦ infectivity and responses, such as MΦ polarization, age, differences in RSV isolates, co-infections, and prior innate priming, are presented. Finally, the review highlights discrepancies observed across experimental models, MΦ origins, and RSV isolates used, complicating the interpretation of MΦ-RSV interactions, thereby underscoring the need for standardized methodologies.