TMEFF1 is a neuron-specific restriction factor for herpes simplex virus.

Autor: Dai Y; Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China., Idorn M; Department of Biomedicine, Aarhus University, Aarhus, Denmark.; Center for Immunology of Viral Infections, Aarhus, Denmark., Serrero MC; Department of Biomedicine, Aarhus University, Aarhus, Denmark.; Center for Immunology of Viral Infections, Aarhus, Denmark., Pan X; Key Laboratory of System Control and Information Processing (Ministry of Education), Institute of Image Processing and Pattern Recognition, Shanghai Jiao Tong University, Shanghai, China., Thomsen EA; Department of Biomedicine, Aarhus University, Aarhus, Denmark.; Center for Immunology of Viral Infections, Aarhus, Denmark., Narita R; Department of Biomedicine, Aarhus University, Aarhus, Denmark.; Center for Immunology of Viral Infections, Aarhus, Denmark., Maimaitili M; Department of Biomedicine, Aarhus University, Aarhus, Denmark.; Center for Immunology of Viral Infections, Aarhus, Denmark., Qian X; School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China., Iversen MB; Department of Biomedicine, Aarhus University, Aarhus, Denmark.; Center for Immunology of Viral Infections, Aarhus, Denmark., Reinert LS; Department of Biomedicine, Aarhus University, Aarhus, Denmark.; Center for Immunology of Viral Infections, Aarhus, Denmark., Flygaard RK; Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark., Chen M; Department of Biomedicine, Aarhus University, Aarhus, Denmark.; Center for Immunology of Viral Infections, Aarhus, Denmark.; Danish Research Institute of Translational Neuroscience, Nordic EMBL Partnership for Molecular Medicine, Aarhus University, Aarhus, Denmark., Ding X; Department of Biomedicine, Aarhus University, Aarhus, Denmark.; Center for Immunology of Viral Infections, Aarhus, Denmark., Zhang BC; Department of Biomedicine, Aarhus University, Aarhus, Denmark.; Center for Immunology of Viral Infections, Aarhus, Denmark., Carter-Timofte ME; Department of Biomedicine, Aarhus University, Aarhus, Denmark.; Center for Immunology of Viral Infections, Aarhus, Denmark., Lu Q; Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Bio-X Institutes, Shanghai Jiao Tong University, Shanghai, China., Jiang Z; Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China., Zhong Y; Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China., Zhang S; Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China., Da L; Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China., Zhu J; Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Bio-X Institutes, Shanghai Jiao Tong University, Shanghai, China., Denham M; Department of Biomedicine, Aarhus University, Aarhus, Denmark.; Danish Research Institute of Translational Neuroscience, Nordic EMBL Partnership for Molecular Medicine, Aarhus University, Aarhus, Denmark., Nissen P; Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark.; Danish Research Institute of Translational Neuroscience, Nordic EMBL Partnership for Molecular Medicine, Aarhus University, Aarhus, Denmark., Mogensen TH; Department of Biomedicine, Aarhus University, Aarhus, Denmark.; Center for Immunology of Viral Infections, Aarhus, Denmark.; Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark., Mikkelsen JG; Department of Biomedicine, Aarhus University, Aarhus, Denmark.; Center for Immunology of Viral Infections, Aarhus, Denmark., Zhang SY; University of Paris, Imagine Institute, Paris, France.; St. Giles Laboratory of Human Genetics of Infectious Diseases, The Rockefeller University, New York, NY, USA., Casanova JL; University of Paris, Imagine Institute, Paris, France.; St. Giles Laboratory of Human Genetics of Infectious Diseases, The Rockefeller University, New York, NY, USA.; Laboratory of Human Genetics of Infectious Diseases, INSERM U1163, Necker Hospital for Sick Children, Paris, France.; Howard Hughes Medical Institute, New York, NY, USA., Cai Y; Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China. yujia.cai@sjtu.edu.cn.; Department of Biomedicine, Aarhus University, Aarhus, Denmark. yujia.cai@sjtu.edu.cn., Paludan SR; Department of Biomedicine, Aarhus University, Aarhus, Denmark. srp@biomed.au.dk.; Center for Immunology of Viral Infections, Aarhus, Denmark. srp@biomed.au.dk.; Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden. srp@biomed.au.dk.
Jazyk: angličtina
Zdroj: Nature [Nature] 2024 Aug; Vol. 632 (8024), pp. 383-389. Date of Electronic Publication: 2024 Jul 24.
DOI: 10.1038/s41586-024-07670-z
Abstrakt: The brain is highly sensitive to damage caused by infection and inflammation 1,2 . Herpes simplex virus 1 (HSV-1) is a neurotropic virus and the cause of herpes simplex encephalitis 3 . It is unknown whether neuron-specific antiviral factors control virus replication to prevent infection and excessive inflammatory responses, hence protecting the brain. Here we identify TMEFF1 as an HSV-1 restriction factor using genome-wide CRISPR screening. TMEFF1 is expressed specifically in neurons of the central nervous system and is not regulated by type I interferon, the best-known innate antiviral system controlling virus infections. Depletion of TMEFF1 in stem-cell-derived human neurons led to elevated viral replication and neuronal death following HSV-1 infection. TMEFF1 blocked the HSV-1 replication cycle at the level of viral entry through interactions with nectin-1 and non-muscle myosin heavy chains IIA and IIB, which are core proteins in virus-cell binding and virus-cell fusion, respectively 4-6 . Notably, Tmeff1 -/- mice exhibited increased susceptibility to HSV-1 infection in the brain but not in the periphery. Within the brain, elevated viral load was observed specifically in neurons. Our study identifies TMEFF1 as a neuron-specific restriction factor essential for prevention of HSV-1 replication in the central nervous system.
(© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
Externí odkaz: