Dataset Information

Phosphoproteome profiling unravels rewiring of chromatin organization factors in host cells upon HBV infection

ABSTRACT: Hepatitis B virus (HBV) infection leads tdevelopment of fatal liver complications. Due to a lack of effective measure to cure HBV infection, complete eradication of HBV is difficult. Thus, novel HBV therapeutic strategies are needed. Host proteins involved in the HBV infection processes are known to be regulated through phosphorylation. System level changes in phospho-signaling pathway in host during infection remains unclear. To this end, phosphoproteome profiling on HBV infected HepG2-NTCP cells was performed.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Hepatocyte, Cell Culture

DISEASE(S): Hepatitis B

SUBMITTER: ZiJie Lim

LAB HEAD: Jayantha Gunaratne

PROVIDER: PXD015393 | Pride | 2022-06-09

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	AWF_Fusion_TMT_MSASPS_Normalization_and_Scaling_phospho.pdAnalysis	Other
	TBP_F_P4_180506_01_IS1153_MSA1.raw	Raw
	TBP_F_P4_180506_02_IS1153_MSA2.raw	Raw
	TBP_F_P4_180506_03_IS1153_MSA3.raw	Raw
	TBP_F_P4_180506_04_IS1153_MSA4.raw	Raw

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Publications

Phosphoproteomics Unravel HBV Triggered Rewiring of Host Phosphosignaling Events.

Lim ZiJie Z Mohd-Ismail Nur Khairiah Binte NKB Png Evelyn E Sze Ching Wooen CW Lin Qifeng Q Hong Wanjin W Lim Seng Gee SG Tan Yee-Joo YJ Gunaratne Jayantha J

International journal of molecular sciences 20220504 9

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-l ...[more]

PMID: 35563518

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Project description:Hepatitis B virus (HBV) causes both acute and chronic liver inflammation. Approximately 600,000 CHB patients each year die of HBV-related diseases such as cirrhosis and liver cancer. Therefore, CHB remains a global health concern. Although there have been anti-HBV agents for treating CHB, they have some limitations including viral-drug resistance and adverse effects. Type III IFN or IFN-λ is promising to use as anti-HBV agents because of its anti-viral activities like type I IFNs. In addition, the expression of its receptor, IFNLR1, is limited only in epithelial cells including hepatocytes. Thus, treatment with IFN-lambda results in less side effects compared to IFN-alpha treatment. IFN-lambdas have been shown to inhibit the replication of several viruses including IAV, DENV, EMCV, HIV, HCV, and HBV; however, there have been no studies on the effects of IFN-λ3, the highest activity among other subtypes, on HBV replication. Therefore, this study aims to determine antiviral activities of IFN-λ3 against HBV replication and to investigate its molecular mechanism responsible for suppressing HBV propagation. The results showed that HBV transcripts and amount of intracellular HBV DNA were decreased in HepG2.2.15 cells, stable HBV-transfected hepatoblastoma cell line, treated with IFN-λ3 in a dose-dependent manner. This indicated that IFN-λ3 could inhibit HBV replication. Next, we performed quantitative proteomics to investigate the proteome changes in HepG2.2.15 treated with IFN-λ3. The proteins that changed their expressions were involved in several biological processes such as defense to viral infection, immune responses, cell-cell adhesion, transcription, translation, and metabolism. We further confirmed the proteomics results by immunoblotting assay. Consistent with MS data, it found that the expression of OAS3, SAMHD1 and STAT1 were increased as a result of IFN-λ3 stimulation. These results indicated that proteomics results were reproducible and reliable. Finally, we proposed 3 possible mechanisms involved in suppressing HBV replication including i.) IFN-λ3 induced anti-viral proteins affecting many steps in HBV life cycle ii.) IFN-λ3 promoted antigen processing and antigen presentation and iii.) IFN-λ3 rescued RIG-I signaling to promote both type I and type III IFN production.

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