{"entity": "researcher", "timestamp": "2026-09-30T03:02:50.137Z", "family": "Reinert", "given": "Line S", "initials": "LS", "orcid": "0000-0002-8317-0886", "affiliations": ["Department of Biomedicine, Aarhus University, Aarhus, Denmark.", "Center for Immunology of Viral Infections, Aarhus University, Aarhus, Denmark."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/9d0252e141874affac713a4f635eb36a.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/9d0252e141874affac713a4f635eb36a"}}, "publications": [{"entity": "publication", "iuid": "ce66d73d81fb49e2b8f008406298ec2b", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/ce66d73d81fb49e2b8f008406298ec2b.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/ce66d73d81fb49e2b8f008406298ec2b"}}, "title": "Deleterious variants in the autophagy-related gene RB1CC1/FIP200 impair immunity to SARS-CoV-2.", "authors": [{"family": "Hu", "given": "Lili", "initials": "L", "orcid": "0009-0000-2653-1713", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/eb398b7f847548de9f7915d8e7829077.json"}}, {"family": "van der Sluis", "given": "Renee M", "initials": "RM", "orcid": "0000-0002-7668-2517", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e36bc23313c5463285762031a7b41850.json"}}, {"family": "Castelino", "given": "Kennith Brian", "initials": "KB", "orcid": "0009-0003-7249-9306", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d143a7feb9974cd19e22619363a39919.json"}}, {"family": "Zhang", "given": "Bao-Cun", "initials": "BC", "orcid": "0000-0001-6104-0848", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/dba7c1a8838749248364aa829a9fe895.json"}}, {"family": "Ronit", "given": "Andreas", "initials": "A"}, {"family": "Zillinger", "given": "Thomas", "initials": "T", "orcid": "0000-0002-0866-4835", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d38c21aaa54f4aa9a416258b4749f06f.json"}}, {"family": "Werner", "given": "Marvin", "initials": "M", "orcid": "0000-0003-1200-807X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/0f88994fd7d44d7ea658bb52fe0d7d38.json"}}, {"family": "J\u00f8rgensen", "given": "Sofie Eg", "initials": "SE"}, {"family": "Hansen", "given": "Anne Louise", "initials": "AL"}, {"family": "Pedersen", "given": "Alice", "initials": "A", "orcid": "0000-0003-4705-8050", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/25507744082240eebea8a3c5eda32ef0.json"}}, {"family": "Narita", "given": "Ryo", "initials": "R", "orcid": "0000-0003-2045-2509", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6027cc559d0d4ceeb1980013e7fcc5c6.json"}}, {"family": "Reinert", "given": "Line S", "initials": "LS", "orcid": "0000-0002-8317-0886", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9d0252e141874affac713a4f635eb36a.json"}}, {"family": "Bundgaard", "given": "Bettina", "initials": "B"}, {"family": "COVID Human Genetic Effort", "given": "", "initials": ""}, {"family": "Holm", "given": "Christian K", "initials": "CK", "orcid": "0000-0002-2655-3362", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8e505f07e4444a5f925522ac90a07134.json"}}, {"family": "Cobat", "given": "Aurelie", "initials": "A", "orcid": "0000-0001-7209-6257", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/55186a4757e7417389f415061b59ab5c.json"}}, {"family": "Casanova", "given": "Jean-Laurent", "initials": "JL"}, {"family": "Reggiori", "given": "Fulvio", "initials": "F"}, {"family": "Mari", "given": "Muriel", "initials": "M", "orcid": "0000-0002-2677-6945", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e82f433912e54a4b87b915c8dbe8c96e.json"}}, {"family": "Paludan", "given": "S\u00f8ren R", "initials": "SR", "orcid": "0000-0001-9180-4060", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/23eddd51092e47d0994535dbaa16096a.json"}}, {"family": "Mogensen", "given": "Trine H", "initials": "TH", "orcid": "0000-0002-1853-9704", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a419fc2fa6c54620900fb1c9c674cc5d.json"}}], "type": "journal article", "published": "2025-11-27", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "16", "issue": "1", "pages": "10618", "issn-l": "2041-1723"}, "abstract": "The clinical outcome of SARS-CoV-2 infection spans from asymptomatic viral elimination to lethal COVID-19 pneumonia, which is due to type I interferon (IFN) deficiency in at least 15-20% of cases. We report two unrelated male patients with critical COVID-19 who are heterozygous for rare deleterious variants in RB1CC1, encoding the autophagy-related FIP200 protein. Airway epithelial cells genetically deprived of FIP200 or cell lines expressing the RB1CC1/FIP200 patient variants exhibit elevated SARS-CoV-2 replication and impaired autophagic flux. The antiviral function of FIP200 is independent of canonical autophagy and type I IFN, but involves the selective autophagy receptor NDP52. We identify a non-canonical function of FIP200 in a novel lysosomal degradation pathway, in which SARS-CoV-2 virions are targeted to single-membrane compartments for degradation of viral RNA in LC3B-positive acidified vesicles. This pathway is impaired in FIP200-deficient cells and in cells expressing FIP200 patient haplotypes. Collectively, we describe a cell-autonomous anti-SARS-CoV-2 restriction pathway, dependent on FIP200 and NDP52, and independent of canonical autophagy and type I IFN, which can underlie critical COVID-19 pneumonia.", "doi": "10.1038/s41467-025-65308-8", "pmid": "41309545", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC12660716"}, {"db": "pii", "key": "10.1038/s41467-025-65308-8"}], "notes": [], "created": "2026-09-23T11:38:38.980Z", "modified": "2026-09-23T11:38:39.621Z"}]}