{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Marcink TC"],"funding":["NIAID NIH HHS","Division of Intramural Research, National Institute of Allergy and Infectious Diseases","Division of Intramural Research, National Institute of Allergy and Infectious Diseases (Division of Intramural Research of the NIAID)"],"pagination":["8831"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11470942"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["15(1)"],"pubmed_abstract":["Paramyxoviruses including measles, Nipah, and parainfluenza viruses are public health threats with pandemic potential. Human parainfluenza virus type 3 (HPIV3) is a leading cause of illness in pediatric, older, and immunocompromised populations. There are no approved vaccines or therapeutics for HPIV3. Neutralizing monoclonal antibodies (mAbs) that target viral fusion are a potential strategy for mitigating paramyxovirus infection, however their utility may be curtailed by viral evolution that leads to resistance. Paramyxoviruses enter cells by fusing with the cell membrane in a process mediated by a complex consisting of a receptor binding protein (HN) and a fusion protein (F). Existing atomic resolution structures fail to reveal physiologically relevant interactions during viral entry. We present cryo-ET structures of pre-fusion HN-F complexes in situ on surfaces of virions that evolved resistance to an anti-HPIV3 F neutralizing mAb. Single mutations in F abolish mAb binding and neutralization. In these complexes, the HN protein that normally restrains F triggering has shifted to uncap the F apex. These complexes are more readily triggered to fuse. These structures shed light on the adaptability of the pre-fusion HN-F complex and mechanisms of paramyxoviral resistance to mAbs, and help define potential barriers to resistance for the design of mAbs."],"journal":["Nature communications"],"pubmed_title":["How a paramyxovirus fusion/entry complex adapts to escape a neutralizing antibody."],"pmcid":["PMC11470942"],"funding_grant_id":["R01 AI121349","AI160961","U19 AI181984","AI160953","R01 AI160953","AI114736","AI121349","AI152275","R01 AI114736","R01 AI160961","F32 AI152275"],"pubmed_authors":["Golub K","Moscona A","Zipursky G","Stearns K","Herman E","Greninger AL","Marcink TC","Sobolik EB","Porotto M"],"additional_accession":[]},"is_claimable":false,"name":"How a paramyxovirus fusion/entry complex adapts to escape a neutralizing antibody.","description":"Paramyxoviruses including measles, Nipah, and parainfluenza viruses are public health threats with pandemic potential. Human parainfluenza virus type 3 (HPIV3) is a leading cause of illness in pediatric, older, and immunocompromised populations. There are no approved vaccines or therapeutics for HPIV3. Neutralizing monoclonal antibodies (mAbs) that target viral fusion are a potential strategy for mitigating paramyxovirus infection, however their utility may be curtailed by viral evolution that leads to resistance. Paramyxoviruses enter cells by fusing with the cell membrane in a process mediated by a complex consisting of a receptor binding protein (HN) and a fusion protein (F). Existing atomic resolution structures fail to reveal physiologically relevant interactions during viral entry. We present cryo-ET structures of pre-fusion HN-F complexes in situ on surfaces of virions that evolved resistance to an anti-HPIV3 F neutralizing mAb. Single mutations in F abolish mAb binding and neutralization. In these complexes, the HN protein that normally restrains F triggering has shifted to uncap the F apex. These complexes are more readily triggered to fuse. These structures shed light on the adaptability of the pre-fusion HN-F complex and mechanisms of paramyxoviral resistance to mAbs, and help define potential barriers to resistance for the design of mAbs.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Oct","modification":"2025-04-04T23:51:09.822Z","creation":"2025-04-04T23:51:09.822Z"},"accession":"S-EPMC11470942","cross_references":{"pubmed":["39396053"],"doi":["10.1038/s41467-024-53082-y"]}}