Deep Proteomic Deconvolution of Interferons and HBV Transfection Effects on a Hepatoblastoma Cell Line
Journal article, 2020

Interferons are commonly utilized in the treatment of chronic hepatitis B virus (HBV) infection but are not effective for all patients. A deep understanding of the limitations of interferon treatment requires delineation of its activity at multiple "omic"levels. While myriad studies have characterized the transcriptomic effects of interferon treatment, surprisingly, few have examined interferon-induced effects at the proteomic level. To remedy this paucity, we stimulated HepG2 cells with both IFN-α and IFN-λ and performed proteomic analysis versus unstimulated cells. Alongside, we examined the effects of HBV transfection in the same cell line, reasoning that parallel IFN and HBV analysis might allow determination of cases where HBV transfection counters the effects of interferons. More than 6000 proteins were identified, with multiple replicates allowing for differential expression analysis at high confidence. Drawing on a compendium of transcriptomic data, as well as proteomic half-life data, we suggest means by which transcriptomic results diverge from our proteomic results. We also invoke a recent multiomic study of HBV-related hepatocarcinoma (HCC), showing that despite HBV's role in initiating HCC, the regulated proteomic landscapes of HBV transfection and HCC do not strongly align. Special focus is applied to the proteasome, with numerous components divergently altered under IFN and HBV-transfection conditions. We also examine alterations of other protein groups relevant to HLA complex peptide display, unveiling intriguing alterations in a number of ubiquitin ligases. Finally, we invoke genome-scale metabolic modeling to predict relevant alterations to the metabolic landscape under experimental conditions. Our data should be useful as a resource for interferon and HBV researchers.

Author

Kenneth Hodge

Chulalongkorn University

Jiradej Makjaroen

Chulalongkorn University

Jonathan Robinson

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology, CSBI

Wallenberg Center for Protein Research (WCPR)

Sakda Khoomrung

Mahidol University

T Pisitkun

Chulalongkorn University

ACS Omega

24701343 (eISSN)

Vol. 5 27 16796-16810

Subject Categories

Immunology in the medical area

Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)

Bioinformatics and Systems Biology

DOI

10.1021/acsomega.0c01865

More information

Latest update

12/9/2020