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The HMGBa-HSP70-ATF4-β Axis Restricts White Spot Syndrome Virus Infection in Crayfish
Xiao-Tong Cao1, Yan Liu1, Jie-Jie Sun2
1College of Veterinary Medicine, Shandong Provincial Key Laboratory of Zoonoses, Shandong Agricultural University, Taian, China.
Abstract:
Envelope viruses are the most threatening pathogens to eukaryotes. The search for target genes against envelope viruses is particularly important. The activating transcription factors (ATFs) regulate cancer proliferation, maintain cellular redox homeostasis, extend biological longevity, and respond to viral stimuli. However, the mechanism of ATF antiviral immunity, especially envelope viruses, is rarely reported. Two ATF4 homologs (ATF4-α and ATF4-β) with a difference of one β sheet (7 amino acids) were identified in crayfish. Further studies showed that ATF4-β was activated and significantly translocated into the nucleus after envelope virus white spot syndrome virus (WSSV) infection. During WSSV infection, the host may recognize WSSV in some way (such as HMGBa recognizing WSSV by interacting with WSSV/VP28) and transmits the signal to cell, and then HMGBa, HSP70, and ATF4-β interact with each other in the cytoplasm and promote nuclear translocation of ATF4-β. ATF4-β entered the nucleus to initiate the transcription of ATF4 and ALFs. In addition, ALF1 could bind to VP28 to inhibit virus assembly in the nucleus and reinfection. This study elucidated a novel mechanism of ATF4-β in antienvelope virus immune responses, and ATF4 may be a potential target for disease prevention and control.
Insights
Activating transcription factors (ATFs) play a role in antiviral immunity. In crayfish, ATF4-β is activated by white spot syndrome virus (WSSV), inhibiting viral replication and offering disease control potential.
Area of Science:
- * Molecular Biology
- * Immunology
- * Virology
Background:
- * Envelope viruses pose significant threats to eukaryotes, necessitating the identification of novel antiviral targets.
- * Activating transcription factors (ATFs) are known to regulate various cellular processes, including responses to viral stimuli, but their specific roles in antiviral immunity against envelope viruses are not well understood.
Purpose of the Study:
- * To investigate the antiviral mechanism of activating transcription factors (ATFs), specifically ATF4 homologs, against envelope viruses in crayfish.
- * To elucidate the role of ATF4-β in the immune response to white spot syndrome virus (WSSV) infection.
Main Methods:
- * Identification and characterization of ATF4 homologs (ATF4-α and ATF4-β) in crayfish.
- * Analysis of ATF4-β activation and nuclear translocation upon WSSV infection.
- * Investigation of protein interactions (HMGBa, HSP70, ATF4-β) involved in signal transduction.
- * Assessment of ALF1's interaction with viral protein VP28 and its effect on virus assembly and reinfection.
Main Results:
- * Two ATF4 homologs, ATF4-α and ATF4-β, were identified in crayfish, differing by a single β sheet.
- * ATF4-β was significantly activated and translocated into the nucleus following WSSV infection.
- * A signaling pathway involving HMGBa, HSP70, and ATF4-β was identified, leading to ATF4-β nuclear translocation.
- * Nuclear ATF4-β initiated the transcription of ATF4 and antiviral literal factors (ALFs).
- * ALF1 was found to bind to WSSV's VP28, inhibiting viral assembly and reinfection.
Conclusions:
- * A novel mechanism of ATF4-β-mediated antiviral immunity against envelope viruses, specifically WSSV, has been elucidated in crayfish.
- * ATF4-β plays a crucial role in the host's defense against WSSV by initiating antiviral gene transcription and its downstream effector ALF1 inhibits viral replication.
- * ATF4 represents a potential therapeutic target for the prevention and control of envelope virus infections.
