2. Academic Validation
  3. ETS Translocation Variant 5 Negatively Modulates Innate Immunity to Facilitate Epstein-Barr Virus Reactivation

ETS Translocation Variant 5 Negatively Modulates Innate Immunity to Facilitate Epstein-Barr Virus Reactivation

  • J Med Virol. 2026 Jan;98(1):e70783. doi: 10.1002/jmv.70783.
Xuefei Liao 1 2,  Mengdi Chen 1 2,  Li Yang 1 2,  Mingjuan Jiang 1 2,  Yujie Xin 1 2,  Huirong Yan 1 2,  Qingshuang Qin 1 2,  Jianhong Lu 1 2 3
Affiliations

Affiliations

  • 1 Department of Microbiology, Xiangya School of Basic Medical Sciences, Central South University, Changsha, Hunan, China.
  • 2 NHC Key Laboratory of Carcinogenesis, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China.
  • 3 Department of Microbiology, School of Basic Medical Sciences, Xinjiang Medical University, Urumqi, China.
PMID: 41459768 DOI: 10.1002/jmv.70783
Abstract

Epstein-Barr virus (EBV) is a member of the gamma-herpesvirus subfamily that is prevalent in the human population. There are two phases of EBV infection: latent Infection and lytic Infection. During lytic reactivation, host innate immune responses are activated to restrict EBV replication. Here, we identified ETS translocation variant 5 (ETV5) as a negative regulator of innate immune responses to facilitate EBV reactivation. ETV5 expression was upregulated by the EBNA1/BRD7 axis, which had been previously described by us, during EBV latent Infection. When EBV was induced into lytic replication, the expression of ETV5 was further increased, and ETV5 overexpression dramatically enhanced the lytic replication of EBV. Mechanistically, upon EBV reactivation, the overexpression of ETV5 suppressed the activation of TANK-binding kinase 1 and interferon regulatory factor 3 (IRF3), as well as the transcription of interferon beta (IFNB1) gene and interferon-stimulated genes (ISGs). The effect of ETV5 knockdown could be reversed by an inhibitor of innate immunity pathway. These findings position ETV5 as a critical accelerator of EBV reactivation through immune evasion, revealing new therapeutic targets for managing EBV-associated diseases.

Keywords

ETV5; Epstein‐Barr virus; innate immune response; reactivation.

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