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

AI Article Synopsis

  • - The research identifies TMEFF1 as a critical factor that helps prevent the replication of the herpes simplex virus type 1 (HSV-1) in neurons, which are particularly vulnerable to damage from infection.
  • - Using CRISPR screening, the study found that TMEFF1 is specifically expressed in central nervous system neurons and works by blocking viral entry, thereby reducing neuronal death during HSV-1 infection.
  • - Experiments showed that mice lacking TMEFF1 were more susceptible to HSV-1 in the brain, highlighting its importance in combating viral infections in the central nervous system.

Article Abstract

The brain is highly sensitive to damage caused by infection and inflammation. Herpes simplex virus 1 (HSV-1) is a neurotropic virus and the cause of herpes simplex encephalitis. 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. 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.

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Source
http://dx.doi.org/10.1038/s41586-024-07670-zDOI Listing

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