| First Author | Dai Y | Year | 2024 |
| Journal | Nature | Volume | 632 |
| Issue | 8024 | Pages | 383-389 |
| PubMed ID | 39048823 | Mgi Jnum | J:354579 |
| Mgi Id | MGI:7734627 | Doi | 10.1038/s41586-024-07670-z |
| Citation | Dai Y, et al. (2024) TMEFF1 is a neuron-specific restriction factor for herpes simplex virus. Nature 632(8024):383-389 |
| abstractText | 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. |
