Methionine enkephalin upregulates the immune function of macrophages to inhibit the infection of Nelson Bay orthoreoviruses (Miyazaki)

Preliminary research has found that MENK can upregulate the antiviral state of macrophages to inhibit influenza virus infection. To further study the immunomodulatory mechanism of MENK in macrophages against reovirus, we used RNA-Seq technology to analyze the genomic changes between macrophages infected with Nelson Bay orthoreoviruses (Miyazaki) after MENK pretreatment and those infected with Miyazaki alone. A total of 3,624 genes were screened, with 1,817 genes upregulated and 1,447 genes downregulated. Differentially expressed genes were mainly enriched in the cell cycle (ko04110), FoxO signaling pathway (ko04068), cell adhesion molecules (ko04514), Fc receptor-mediated endocytosis (ko04666), and antigen processing and presentation pathways (ko04612). Key genes such as IL6ST, TNFR2, CCL24, MHC I, MHC II, CD28, FOXO-1, SYK, BCL-XL, and CYCD1 were successfully docked with the MENK molecule. Genomic analysis showed that MENK enhanced the immune function of macrophages by upregulating cytokine-related molecules such as CCL24, IL6ST, and TNFR2 to recruit and induce inflammatory responses. Moreover, MENK upregulated the expression of MHC I, MHC II, and CD28 to promote antigen presentation and initiate adaptive immune responses and regulated the FoxO-CycD1 pathway to inhibit the cell cycle, thereby exerting antiviral effects during reovirus infection.