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Mechanistic Insights into the Suppression of EBV Lytic Replication by Sanyang Toujie Decoction in Pediatric Infectious Mononucleosis

ABSTRACT: Infection with Epstein-Barr virus (EBV) usually results in asymptomatic infection in the pediatric population. In some pediatric patients, it can lead to infectious mononucleosis (IM) and may be complicated by malignant diseases such as hemophagocytic lymphohistiocytosis (HLH) and chronic active EBV infection (CAEBV). The traditional Chinese medicine (TCM) Sanyang Toujie Decoction (SYTJ) exerts a favorable therapeutic effect on IM associated with EBV infection. However, its active components and underlying mechanisms of action remain unclear. ObjectiveTo clarify the mechanisms of SYTJ against EBV infection in the treatment of pediatric IM by integrating multi-omics and molecular biology approaches. Study DesignWe collected serum samples from healthy children undergoing routine physical examinations, pediatric patients with IM, and pediatric IM patients after SYTJ treatment. An innovative strategy combining proteomics, metabolomics, and molecular biology was adopted to investigate the active components and mechanisms of action of SYTJ. We explored the anti-EBV targets, biological processes, and pathways of SYTJ at the metabolite and protein levels, and established an EBV lytic infection model for validation. ResultsA total of 1,424 chemical components were identified in the fingerprint of SYTJ. Multi-omics and systems biology analyses revealed that the pharmacological mechanisms of SYTJ involve 34 core proteins and 6 core differential metabolites, which are enriched in EBV infection-related key pathways including the Toll-like receptor signaling pathway, glycerophospholipid metabolism, and pentose phosphate pathway. Validation experiments demonstrated that SYTJ could inhibit the proliferation of RAJI and B95-8 cells, promote cell apoptosis, reduce the expression of EBV-EA in RAJI cells and EBV-VCA in B95-8 cells, and suppress EBV-DNA replication. In addition, SYTJ downregulated the mRNA and protein expression of BZLF1 and BMRF1 in B95-8 cells, inhibited EBV lytic replication, upregulated the expression of TOLLIP protein, and suppressed the TLR9/MYD88/NF-κB pathway. ConclusionSYTJ can reduce EBV lytic replication, upregulate TOLLIP protein expression, inhibit the TLR9/MYD88/NF-κB pathway, and alleviate the immune-inflammatory response in the body.

ORGANISM(S): Homo Sapiens

SUBMITTER: Yongbin Yan

PROVIDER: PXD071703 | iProX | Sun Dec 07 00:00:00 GMT 2025

REPOSITORIES: iProX

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Mechanistic Insights into the Suppression of EBV Lytic Replication by Sanyang Toujie Decoction in Pediatric Infectious Mononucleosis

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