Extensive Proteomic Approach to Assess Protein Alterations in Human Hepatoma Huh7 Cells Infected with West Nile Virus
- 1Functional Proteomics Lab, Department of Life Sciences, University of Siena, 53100 Siena, Italy
- 2Medical Biotechnologies Department, University of Siena, 53100 Siena, Italy
- 3Departmental Faculty, UniCamillus, Saint Camillus International University of Health Sciences, Via di Sant’Alessandro, 8, 00131 Rome, Italy
Abstract
West Nile Virus (WNV) is a significant global health threat, and the molecular mechanisms of its pathogenic activity in human hosts remain partially understood. This study applies an extensive proteomic approach combining “top-down” (2DE/MS) and “bottom-up” (LC-MS/MS) technologies to investigate protein changes in the Huh7 human hepatoma cellular model at 48 h post-infection with WNV. Our results demonstrate that WNV infection induces a massive downregulation of host proteins, particularly those involved in cell–cell adhesion and extracellular matrix (ECM) integrity (FN1, VTN, desmosome proteins and tight junctional proteins), which supports theories of blood–brain barrier disruption. Moreover, we highlighted a modulation of iron homeostasis (FTH1, IRP1, and IREB2) reflecting a “nutritional immunity” host response aimed at limiting host enzyme functions essential for virus replication. In particular, the top-down approach demonstrated a significant protein species modulation related to the unfolded protein response (UPR) (HSP90, HSPA8), as well as the hijacking of translation initiation factors (EIF1, eIF3 complex, and EIF4A1), which suggests viral strategies for immune evasion and efficient replication. Taken together, these findings offer a comprehensive overview of WNV-induced perturbations, revealing the quantitative modulation of proteins and potential post-translational signatures, thereby providing a robust foundation for identifying new antiviral drug targets and therapeutic strategies.
Related
- Transcriptome Analysis of Hepatitis C Virus-Infected Hepatoma Cells Following Stringent Removal of Genomic DNA.
- Temporal Proteomic Characterization of SARS-CoV-2-Infected Mouse Lungs
- Subclinical hepatorenal biomarker alterations and urogenital indicators in Schistosoma haematobium-infected School-Aged Children in Sene West District, Ghana
- Carbon starvation of Mycobacterium abscessus induces a non-replicating state with extensive proteomic remodeling
- Beyond Classical Reward Circuits: Dorsal Striatum Proteomic Alterations in an Adolescent Phencyclidine-Induced Mouse Model of Schizophrenia and Nicotine Use
BibTeX
@article{shaba2026extensive,
title = {{Extensive Proteomic Approach to Assess Protein Alterations in Human Hepatoma Huh7 Cells Infected with West Nile Virus}},
author = {Enxhi Shaba and Claudia Landi and Ilaria Vicenti and Lorenza Vantaggiato and Francesco Saladini and Camilla Biba and Niccolò Bartolini and Maurizio Zazzi and Luca Bini},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27209387},
url = {https://www.mdpi.com/1422-0067/27/20/9387},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Extensive Proteomic Approach to Assess Protein Alterations in Human Hepatoma Huh7 Cells Infected with West Nile Virus
AU - Enxhi Shaba
AU - Claudia Landi
AU - Ilaria Vicenti
AU - Lorenza Vantaggiato
AU - Francesco Saladini
AU - Camilla Biba
AU - Niccolò Bartolini
AU - Maurizio Zazzi
AU - Luca Bini
PY - 2026
DA - 2026/10/21
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27209387
UR - https://www.mdpi.com/1422-0067/27/20/9387
AB - West Nile Virus (WNV) is a significant global health threat, and the molecular mechanisms of its pathogenic activity in human hosts remain partially understood. This study applies an extensive proteomic approach combining “top-down” (2DE/MS) and “bottom-up” (LC-MS/MS) technologies to investigate protein changes in the Huh7 human hepatoma cellular model at 48 h post-infection with WNV. Our results demonstrate that WNV infection induces a massive downregulation of host proteins, particularly those involved in cell–cell adhesion and extracellular matrix (ECM) integrity (FN1, VTN, desmosome proteins and tight junctional proteins), which supports theories of blood–brain barrier disruption. Moreover, we highlighted a modulation of iron homeostasis (FTH1, IRP1, and IREB2) reflecting a “nutritional immunity” host response aimed at limiting host enzyme functions essential for virus replication. In particular, the top-down approach demonstrated a significant protein species modulation related to the unfolded protein response (UPR) (HSP90, HSPA8), as well as the hijacking of translation initiation factors (EIF1, eIF3 complex, and EIF4A1), which suggests viral strategies for immune evasion and efficient replication. Taken together, these findings offer a comprehensive overview of WNV-induced perturbations, revealing the quantitative modulation of proteins and potential post-translational signatures, thereby providing a robust foundation for identifying new antiviral drug targets and therapeutic strategies.
SN - 1422-0067
ER -