ArticleFrontiers in microbiology2026
Unraveling the dual immunomodulatory and immunogenic roles of the central conserved cysteine-rich region in respiratory syncytial virus G protein.
Article in Frontiers in microbiology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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Who cites it
1 citing paper in PubMed.
- Therapeutic potential of nutritional aryl hydrocarbon receptor ligands for respiratory syncytial virus infection: a mini review.Frontiers in microbiology · 2026Review
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Authors and funding
18 authors.
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Abstract
Background: Respiratory syncytial virus (RSV) causes severe respiratory disease in infants and high-risk adults, in part by subverting host immunity. The RSV G glycoprotein's central conserved cysteine rich domain (CCD) contains a CX3C motif implicated in immune modulation, but the relationship between its redox state, structural conformation, and immune modulatory function remains unclear. Methods: In this study, we recombinantly expressed a CCD-derived peptide (Gpep, residues 149-196), determined its redox-dependent folding by reversed-phase HPLC (RP-HPLC) and biophysical analyses, and assessed its function using murine dendritic cell and human neutrophil assays alongside pediatric serology. Results: Kinetic analyses by RP‑HPLC and biophysical techniques showed that reduced Gpep rapidly folds through a predominant intermediate to yield an oxidized monomer; conversely, higher concentrations drive intermolecular disulfide isomerization and covalent oligomer formation. Functionally, Gpep inhibited dendritic cell activation elicited by both LPS- and UV-inactivated RSV. In addition, Gpep suppressed multiple human neutrophil responses, including chemotaxis, CD11b upregulation, reactive oxygen species production, myeloperoxidase release, and NET formation, without inducing cytotoxicity. In contrast, oligomerized Gpep lacked immunosuppressive activity. Serological analysis of an ambulatory pediatric cohort (0-72 months) showed a transient increase in the anti-F/anti-G IgG ratio following early RSV exposures, consistent with preferential maturation of F-directed responses. Discussion: We propose a redox‑dependent immune‑evasion model in which secreted, monomeric G mediates transient immunosuppression that is halted by disulfide‑driven oligomerization of membrane‑bound G and F proteins. These findings support a mechanistic association between the redox state of RSV G, its oligomeric behavior, and its immunomodulatory properties.
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