Research Assistant University of Florida Gainesville, Florida, United States
Disclosure(s):
Julie Murphy, Bachelors: No financial relationships to disclose
Introduction/Rationale: The mammalian protein suppressor of cytokine signaling 1 (SOCS1), can inhibit the activity of Janus Kinase 2 (Jak2), serving to critically limit the magnitude and duration of inflammatory processes and prevent autoimmunity. SOCS1 can be hijacked by viruses, such as SARS-CoV-2, and cancers to prevent Jak2-mediated detection and elimination. Notably, a peptide corresponding to the activation loop of JAK2, pJAK2(1001–1013), has been shown to act as a decoy for SOCS1 binding and suppresses SOCS1 activity. However, the ability of the SOCS1 antagonist, pJAK2(1001–1013), to restore cellular immune responses and enhance viability in response to SARS-CoV-2 infection remains unclear.
Methods: To evaluate this, we assessed viability (crystal violet), viral replication (confocal microscopy), and gene expression (qPCR) of baby hamster kidney (BHK) cells expressing the human ACE-2 receptor with a laboratory safe SARS-CoV-2 pseudo virus with and without pJAK2 treatment.
Results: Based on our findings, the SOCS1 antagonist peptide decreased cell death caused by SARS-CoV-2 infection. Treatment with pJAK2 also reduced viral replication compared to cells without treatment. Preliminary findings indicate that pJAK2 can significantly enhance gene expression of proinflammatory cytokines such as IL-1, IL-6, and TNF.
Conclusion: These results suggest that the antagonist peptide has potential as a therapeutic agent against SARS-CoV-2 infection, or cancers, by enhancing cell viability and boosting immune responses through activation of the JAK/STAT signaling pathway. Future research will investigate the effects of pJAK2 on viral entry and replication using flow cytometry.
