The role of the TRAF6-Akt axis in the life cycle of oncogenic herpesviruses is highlighted and potential therapeutic targets for related diseases are suggested.
Abstract
TRAF6 is traditionally recognized as an antiviral ubiquitin E3 ligase that positively regulates the production of type I interferon and inflammatory cytokines. However, our study reveals that TRAF6 also plays a crucial role in the lytic replication of Kaposi’s sarcoma-associated herpesvirus (KSHV). Mechanistically, during KSHV lytic replication, TRAF6 mediates the K63-linked polyubiquitination and activation of Akt, which is required for the efficient viral replication. Disruption of TRAF6 or Akt expression through CRISPR-mediated knockout, or inhibition of TRAF6 or Akt with small molecule inhibitors, reduces KSHV replication efficiency. Conversely, expression of constitutively active Akt can rescue the impaired replication caused by TRAF6 deficiency. Notably, the TRAF6-Akt axis is also required for the lytic replication of Epstein-Barr virus but not for Human cytomegalovirus. These findings highlight the role of the TRAF6-Akt axis in the life cycle of oncogenic herpesviruses and suggest potential therapeutic targets for related diseases.
ABSTRACT Autophagy-associated protein 13 (ATG13) plays a pivotal role in regulating the assembly of the autophagy initiation complex. However, the function and mechanism of action of ATG13 during influenza virus infection remain incompletely understood. This study elucidates that ATG13 restricts influenza A virus (IAV)...
Yi-Yuan Lu, Jia-Le Chen, Hui-Ming Xiao et al.· Emerging Microbes and Infect...· 0 citations
The mitochondrial antiviral signaling protein (MAVS; also known as VISA, IPS-1, or Cardif) is the central adaptor of the RIG-I-like receptor (RLR) pathway. Upon viral infection, MAVS forms prion-like aggregates to activate NF-κB and IRF3, thereby inducing type I interferon production and antiviral responses. Here, we i...
De-Ping Kong, N. Zhong, Jie Zhang et al.· Journal of Medical Virology· 0 citations
It is indicated that EcSrc promotes NF-κB-associated antiviral responses against SGIV and an EcSrc-TRAF5 interaction potentially involved in teleost antiviral immunity is identified and identified.
Lingfeng Guan, Yi Li, Ting Yu et al.· Fish and Shellfish Immunolog...· 0 citations
The E3 ubiquitin ligase TRIM23 is involved in diverse cellular processes, however, its function in antiviral defense against adenovirus remains unclear. Here, we identify a novel mechanism by which TRIM23 restricts human adenovirus type 5 (HAdV-C5) replication. TRIM23 expression was upregulated upon HAdV-C5 infection,...
Nan Sun, Ji-Kai Zhang, Ban-Ruo Xia et al.· PLoS Pathogens· 0 citations
These findings reveal a proviral strategy whereby PRV UL40 hijacks EphA2 to counteract an intrinsic Akt-dependent inhibitory pathway, and EphA2 S897 represents a potential therapeutic target for mitigating alphaherpesvirus immunopathology.
Yutong Tian, Hang Yin, Jia-Xiang Fu et al.· Veterinary Research· 0 citations
An autophagy-dependent antiviral mechanism is uncovered, IDOL is established as an innate immune regulator with a non-canonical function, and a viral immune evasion strategy is defined, positioning IDOL as a promising therapeutic target for PRRSV control.
