Deep Proteomic Deconvolution of Interferons and HBV
Transfection Effects on a Hepatoblastoma Cell Line
Posted on 2020-06-26 - 18:11
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.
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Hodge, Kenneth; Makjaroen, Jiradej; Robinson, Jonathan; Khoomrung, Sakda; Pisitkun, Trairak (2020). Deep Proteomic Deconvolution of Interferons and HBV
Transfection Effects on a Hepatoblastoma Cell Line. ACS Publications. Collection. https://doi.org/10.1021/acsomega.0c01865