Proteomic changes in HEK-293 cells induced by hepatitis delta virus replication

Area of Science:

• * Virology
• * Molecular Biology
• * Proteomics

Background:

• * Hepatitis delta virus (HDV) significantly elevates hepatocellular carcinoma (HCC) risk in chronic hepatitis B virus (HBV) patients.
• * HDV replication relies on host factors, but these and its pathogenic mechanisms remain largely unknown.
• * Understanding HDV's impact on host cells is crucial for developing targeted therapies.

Purpose of the Study:

• * To investigate proteomic changes in host cells during HDV replication.
• * To identify host factors and pathways affected by HDV.
• * To elucidate mechanisms linking HDV infection to HCC.

Main Methods:

• * Engineered HEK-293 cells to mimic HDV replication.
• * Employed MS-based quantitative proteomics with (18)O/(16)O stable isotope labeling.
• * Utilized systems biology approaches to analyze altered pathways and networks.

Main Results:

• * Quantified ~3000 proteins, identifying 89 differentially expressed proteins due to HDV RNA replication.
• * Validated down-regulation of p53, HSPE, ELAV and up-regulation of Transportin 1, EIF3D, Cofilin 1.
• * Identified G2/M DNA damage checkpoint and pyruvate metabolism as significantly affected pathways; Cancer as the most probable associated disease.

Conclusions:

• * HDV replication induces significant changes in the host cell proteome.
• * Disruption of the G2/M cell cycle control checkpoint, evidenced by down-regulated 14-3-3 σ interactor, is a key finding.
• * These findings offer new insights into HDV-associated HCC pathogenesis.