کنگره بین المللی زیست فناوری گیاهان دارویی و قارچ های کوهی

صفحه اصلی / پنجمین کنگره بین المللی و ششمین همایش ملی زیست فناوری گیاهان دارویی و قارچ های کوهی

Multi-Omics Modeling of Immune Pathways Induced by Shiitake Mushroom AHCC in the Sustained Clearance of HPV Using the Nucleotide Transformer

نویسندگان :

Shayan Shirazian¹ Nayereh Akbari² Maryamalsadat Gazeri³

1- دانشگاه علم و فرهنگ تهران 2- دانشگاه ارومیه 3- دانشگاه آزاد اسلامی واحد علوم پزشکی تهران

کلمات کلیدی :

HPV،Shiitake،AHCC،Bioinformatics،Nucleotide Transformer،Antiviral Immunity،Deep Learning

چکیده :

Human papillomavirus (HPV) persistence is linked to dysregulation of interferon (IFN) pathways, where IFN-γ plays a key role in antiviral and antitumor immunity by coordinating NK cells, T cells, and antigen-presenting cells(Barrat et al., 2019; Bhat et al., 2018; Castro et al., 2018. Clinical studies show that Active Hexose Correlated Compound (AHCC), a shiitake mushroom extract, supports HPV clearance by enhancing both innate and adaptive immunity(Smith et al., 2022), modulating dendritic and regulatory T cell function(Chowdhury et al., 2019), and promoting Th1-biased, IFN-γ–driven responses(Dea-Ayuela et al., 2020). Additionally, AHCC’s effects may extend to PD-1/PD-L1 checkpoint regulation, influencing viral clearance versus immune evasion(Gao et al., 2018; Sun et al., 2018). Collectively, evidence suggests that AHCC fosters a favorable immune environment for HPV elimination. In this study, we employed an advanced bioinformatics pipeline integrating transcriptomics, metabolomics, and immunomics datasets to construct a predictive framework for identifying key immune pathways activated in response to AHCC. Promoter sequences of immune-related genes were extracted and analyzed using the Nucleotide Transformer genomic language model to uncover structural and regulatory features influencing gene expression under treatment versus control conditions. Subsequently, deep learning algorithms and network-based pathway analyses were applied to integrate multi-omics data, revealing candidate genes and central hubs within IFN-γ signaling, NK cell activation and PD-1/PD-L1 immune checkpoint pathways. Our modeling results suggest that AHCC enhances antiviral immunity against HPV by modulating the expression of critical genes associated with Th1-biased immune responses. This work not only provides novel insights into the molecular immunomodulatory mechanisms of shiitake-derived AHCC in HPV clearance but also establishes a data-driven framework for developing next-generation adjuvant therapies based on medicinal mushrooms.