p62-Mediated Selective Autophagy Attenuates cGAS-STING Signaling in EBV Latency
Abstract
The interferon regulatory factors (IRFs) and type I interferons (IFNs) play crucial roles in Epstein-Barr Virus (EBV) pathologies. The cGAS-STING pathway is critical for the induction of type I IFNs through IRF3 in response to double-stranded DNA (dsDNA). In this study, we found that both cGAS and STING are highly expressed in EBV+ B cells with type III latency compared to type I latency. However, these type III cells display minimal type I IFN induction following treatment with the potent STING agonist diABZI. We observed that treatment with Bafilomycin A1, an inhibitor of lysosomal acidification, impaired STING degradation following diABZI stimulation, suggesting that STING is degraded via an autophagy-dependent pathway. Further investigation revealed that the selective autophagy receptor p62 is involved in suppressing STING activity during EBV latency. Depletion of p62 via specific shRNAs in EBV-transformed cells resulted in a dramatic increase in p-IRF3 (S396) and IFN-β production upon diABZI treatment. Additionally, co-immunoprecipitation confirmed that p62 and STING physically interact. Building on our previous finding that p62-selective autophagy depends on mitochondrial reactive oxygen species (ROS) in EBV latency, our preliminary data suggest that quenching ROS with N-acetylcysteine amide (NACA) or MitoQ increases diABZI-induced STING activation while downregulates p62-selective autophagy activity. These results strongly suggest that the ROS-p62 signaling axis attenuates the cGAS-STING-IRF3-mediated immune response. Future studies will further elucidate how the EBV oncoprotein latent membrane protein 1 (LMP1) orchestrates this immune evasion strategy.
Start Time
15-4-2026 9:00 AM
End Time
15-4-2026 12:00 PM
Room Number
Culp Ballroom 316
Poster Number
39
Presentation Type
Poster
Presentation Subtype
Posters - Competitive
Presentation Category
Health
Student Type
Graduate and Professional Degree Students, Residents, Fellows
Faculty Mentor
Shunbin Ning
p62-Mediated Selective Autophagy Attenuates cGAS-STING Signaling in EBV Latency
Culp Ballroom 316
The interferon regulatory factors (IRFs) and type I interferons (IFNs) play crucial roles in Epstein-Barr Virus (EBV) pathologies. The cGAS-STING pathway is critical for the induction of type I IFNs through IRF3 in response to double-stranded DNA (dsDNA). In this study, we found that both cGAS and STING are highly expressed in EBV+ B cells with type III latency compared to type I latency. However, these type III cells display minimal type I IFN induction following treatment with the potent STING agonist diABZI. We observed that treatment with Bafilomycin A1, an inhibitor of lysosomal acidification, impaired STING degradation following diABZI stimulation, suggesting that STING is degraded via an autophagy-dependent pathway. Further investigation revealed that the selective autophagy receptor p62 is involved in suppressing STING activity during EBV latency. Depletion of p62 via specific shRNAs in EBV-transformed cells resulted in a dramatic increase in p-IRF3 (S396) and IFN-β production upon diABZI treatment. Additionally, co-immunoprecipitation confirmed that p62 and STING physically interact. Building on our previous finding that p62-selective autophagy depends on mitochondrial reactive oxygen species (ROS) in EBV latency, our preliminary data suggest that quenching ROS with N-acetylcysteine amide (NACA) or MitoQ increases diABZI-induced STING activation while downregulates p62-selective autophagy activity. These results strongly suggest that the ROS-p62 signaling axis attenuates the cGAS-STING-IRF3-mediated immune response. Future studies will further elucidate how the EBV oncoprotein latent membrane protein 1 (LMP1) orchestrates this immune evasion strategy.
