Phosphoproteomics Unravel HBV Triggered Rewiring of Host Phosphosignaling Events

• Published in: International journal of molecular sciences Vol. 23; no. 9; p. 5127
• Main Authors: Lim, ZiJie, Mohd-Ismail, Nur Khairiah Binte, Png, Evelyn, Sze, Ching Wooen, Lin, Qifeng, Hong, Wanjin, Lim, Seng Gee, Tan, Yee-Joo, Gunaratne, Jayantha
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 04.05.2022; MDPI
• Subjects: Antigens; Cell cycle; Computer applications; Disease control; Genomes; Granulocytes; Hep G2 Cells; Hepatitis B; hepatitis B virus; Hepatitis B virus - genetics; Hepatocytes - metabolism; Humans; Immune response; Immune system; Infections; kinase inhibitor; Kinases; kinome; Liver cancer; Localization; MAP kinase; Organic Anion Transporters, Sodium-Dependent - metabolism; phosphoproteomics; Phosphorylation; phosphosignaling; Protein kinase A; Protein-tyrosine kinase; Proteins; Public health; RNA processing; Symporters - metabolism; Tyrosine; Viral infections; phosphoproteomics; kinase inhibitor; phosphosignaling; kinases; hepatitis B virus; kinome
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms23095127

Hepatitis B virus (HBV) infection persists as a major global health problem despite the availability of HBV vaccines for disease prevention. However, vaccination rates remains low in some regions of the world, driving the need for novel strategies to minimise infections and prevent disease progression. Thus, understanding of perturbed molecular signaling events during early phases of HBV infection is required. Phosphosignaling is known to be involved in the HBV infection processes, yet systems-level changes in phosphosignaling pathways in the host during infection remain unclear. To this end, we performed phosphoproteome profiling on HBV-infected HepG2-NTCP cells. Our results showed that HBV infection drastically altered the host phosphoproteome and its associated proteins, including kinases. Computational analysis of this phosphoproteome revealed dysregulation of the pathways involved in immune responses, cell cycle processes, and RNA processing during HBV infection. Kinase Substrate Enrichment Analysis (KSEA) identified the dysregulated activities of important kinases, including those from CMGC (CDK, MAPK, GSK, and CLK), AGC (protein kinase A, G, and C), and TK (Tyrosine Kinase) families. Of note, the inhibition of CLKs significantly reduced HBV infection in HepG2-NTCP cells. In all, our study unravelled the aberrated phosphosignaling pathways and the associated kinases, presenting potential entry points for developing novel therapeutic strategies for HBV treatment.