Phosphoproteomics Unravel HBV Triggered Rewiring of Host Phosphosignaling Events

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Phosphoproteomics Unravel HBV Triggered Rewiring of Host Phosphosignaling Events
Title:
Phosphoproteomics Unravel HBV Triggered Rewiring of Host Phosphosignaling Events
Journal Title:
International Journal of Molecular Sciences
Keywords:
Publication Date:
05 May 2022
Citation:
Lim, Z., Mohd-Ismail, N. K. B., Png, E., Sze, C. W., Lin, Q., Hong, W., Lim, S. G., Tan, Y.-J., & Gunaratne, J. (2022). Phosphoproteomics Unravel HBV Triggered Rewiring of Host Phosphosignaling Events. International Journal of Molecular Sciences, 23(9), 5127. https://doi.org/10.3390/ijms23095127
Abstract:
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.
License type:
Attribution 4.0 International (CC BY 4.0)
Funding Info:
This research / project is supported by the National Medical Research Council (NMRC) - TCR Flagship programme, Eradication of Chronic Hepatitis B
Grant Reference no. : NMRC/TCR/014-NUHS/2015

This research / project is supported by the National Medical Research Council (NMRC) - NMRC Open Fund Large Collaborative Grant (OFLCG), Achieving Functional Cure of Chronic Hepatitis B
Grant Reference no. : MOH-OFLCG19May-0005
Description:
ISSN:
1422-0067