Analysis of Fasciola Hepatica Hdm-1 Mrna Expression Across Developmental Stages and Computational Simulation of Its Internalization Pathway Publisher



Malekzade P ; Fathi S ; Hosseini SH ; Moghadasi AN ; Shahbakhsh M ; Shayan P ; Rismani E ; Jalousian F
Source: Journal of Zoonotic Diseases Published:2025

Abstract

FhHDM-1(Fasciola hepatica Helminth Defense Molecule-1) plays a role in the ability of Fasciola spp., to evade the host’s immune system. Here, the transcription of FhHDM-1 was shown in the developmental stages of Fasciola hepatica (F.hepatica). We simulated peptide initialization by the Linux operating system using GROningen Machine for Chemical Simulations (GROMACS) and Coarse-grained molecular dynamics (CGMD) Simulation. The final structure of the peptide was extracted from the last frame of the simulation and used as the initial structure for the simulation of protein initialization into the plasma membrane. All HDM clade sequences showed amino acid sequence identity in the sequence part of HDMs, consisting of an N-terminal signal peptide, and a C-terminal amphipathic motif when compared with orthologues from other trematodes in databases. Stereo chemical structures and biochemical features of peptides, were provided for protein biological expression systems. Our findings revealed the presence of FhHDM-1 mRNA in F. hepatica adult flukes and the lack of mRNA in its eggs and miracidia, indicating its central role in the evolution of the parasitic life cycle. The internalization of the peptide into the plasma membrane lipid rafts by the polar heads of lipid molecules and interaction with phospholipids, in turn, results in creating curvature, leading to endocytosis pathways. The possible presenting antigens by MHC classes I and II were identified as overlapping fragments. Its capability to enter macrophages and suppress lysosomal acidification indicates its potential as a therapeutic agent for inflammatory diseases, alongside its ability to present epitopes through MHC-I and MHC-II pathways. © 2025, Published by the University of Tabriz.