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A deep understanding of the limitations of interferon treatment requires delineation of its activity at multiple \u201comic\u201d 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-\u03b1 and IFN-\u03bb 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\u2019s 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.<\/jats:p>","DOI":"10.1021\/acsomega.0c01865","type":"journal-article","created":{"date-parts":[[2020,6,27]],"date-time":"2020-06-27T02:47:20Z","timestamp":1593226040000},"page":"16796-16810","source":"Crossref","is-referenced-by-count":5,"title":["Deep Proteomic Deconvolution of Interferons and HBV\nTransfection Effects on a Hepatoblastoma Cell Line"],"prefix":"10.1021","volume":"5","author":[{"given":"Kenneth","family":"Hodge","sequence":"first","affiliation":[{"name":"Chulalongkorn University , , 1873 Rama 4 Road , Pathumwan, ,","place":["Bangkok, Thailand, 10330"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiradej","family":"Makjaroen","sequence":"additional","affiliation":[{"name":"Chulalongkorn University , , 1873 Rama 4 Road , Pathumwan, ,","place":["Bangkok, Thailand, 10330"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8567-5960","authenticated-orcid":true,"given":"Jonathan","family":"Robinson","sequence":"additional","affiliation":[{"name":"Chalmers University of Technology , , Kemiva\u0308gen 10 , ,","place":["Gothenburg, Sweden, 412 96"]},{"name":"Chalmers University of Technology , , Kemiva\u0308gen 10 , ,","place":["Gothenburg, Sweden, 412 96"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9461-8597","authenticated-orcid":true,"given":"Sakda","family":"Khoomrung","sequence":"additional","affiliation":[{"name":"Mahidol University , , ,","place":["Bangkok, Thailand, 10700"]},{"name":"Mahidol University , , Rama 6 Road , ,","place":["Bangkok, Thailand, 10400"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2451-0318","authenticated-orcid":true,"given":"Trairak","family":"Pisitkun","sequence":"additional","affiliation":[{"name":"Chulalongkorn University , , 1873 Rama 4 Road , Pathumwan, ,","place":["Bangkok, Thailand, 10330"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2020,6,26]]},"reference":[{"key":"2026090210011631100_cit1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0009753","article-title":"Dissecting\ninterferon-induced\ntranscriptional programs in human peripheral blood cells","volume":"5","author":"Waddell","year":"2010","journal-title":"PLoS One"},{"key":"2026090210011631100_cit2","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1038\/sj.cr.7290309","article-title":"The host type\nI interferon response to viral and bacterial infections","volume":"15","author":"Perry","year":"2005","journal-title":"Cell Res."},{"key":"2026090210011631100_cit3","doi-asserted-by":"publisher","first-page":"719","DOI":"10.1128\/iai.47.3.719-722.1985","article-title":"Interferon-induced inhibition of Chlamydia trachomatis:\ndissociation from antiviral and antiproliferative effects","volume":"47","author":"de la Maza","year":"1985","journal-title":"Infect. Immun."},{"key":"2026090210011631100_cit4","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1016\/j.pt.2014.07.007","article-title":"Protozoan\nparasites and type I interferons: a cold case reopened","volume":"30","author":"Beiting","year":"2014","journal-title":"Trends Parasitol."},{"key":"2026090210011631100_cit5","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1038\/nri3787","article-title":"Type I interferons\nin infectious disease","volume":"15","author":"McNab","year":"2015","journal-title":"Nat. Rev. Immunol."},{"key":"2026090210011631100_cit6","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1089\/jir.2013.0158","article-title":"How type I interferons work in multiple sclerosis and other diseases:\nsome unexpected mechanisms","volume":"34","author":"Reder","year":"2014","journal-title":"J. Interferon Cytokine\nRes."},{"key":"2026090210011631100_cit7","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1038\/nrc.2016.14","article-title":"Antitumour\nactions of interferons:\nimplications for cancer therapy","volume":"16","author":"Parker","year":"2016","journal-title":"Nat. Rev. Cancer"},{"key":"2026090210011631100_cit8","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1093\/nar\/30.1.207","article-title":"Gene Expression\nOmnibus: NCBI gene\nexpression and hybridization array data repository","volume":"30","author":"Edgar","year":"2002","journal-title":"Nucleic Acids Res."},{"key":"2026090210011631100_cit9","doi-asserted-by":"publisher","first-page":"1139","DOI":"10.3389\/fimmu.2017.01139","article-title":"Deciphering\nof the Human Interferon-Regulated Proteome by Mass Spectrometry-Based\nQuantitative Analysis Reveals Extent and Dynamics of Protein Induction\nand Repression","volume":"8","author":"Megger","year":"2017","journal-title":"Front. 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Biochem."},{"key":"2026090210011631100_cit22","doi-asserted-by":"publisher","first-page":"6669","DOI":"10.1073\/pnas.0401771101","article-title":"Genomic analysis\nof the host response to hepatitis B virus infection","volume":"101","author":"Wieland","year":"2004","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2026090210011631100_cit23","doi-asserted-by":"publisher","first-page":"9369","DOI":"10.1128\/jvi.79.15.9369-9380.2005","article-title":"Stealth and cunning: hepatitis B and hepatitis C viruses","volume":"79","author":"Wieland","year":"2005","journal-title":"J. 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Immunol."},{"key":"2026090210011631100_cit27","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0022200","article-title":"USP18-based\nnegative feedback control is induced by type I and type III interferons\nand specifically inactivates interferon alpha response","volume":"6","author":"Franc\u0327ois-Newton","year":"2011","journal-title":"PLoS One"},{"key":"2026090210011631100_cit28","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1016\/j.chom.2007.06.009","article-title":"The interferon-inducible\nprotein\nviperin inhibits influenza virus release by perturbing lipid rafts","volume":"2","author":"Wang","year":"2007","journal-title":"Cell Host Microbe"},{"key":"2026090210011631100_cit29","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1038\/s41467-018-03106-1","article-title":"Systematic\nanalysis of protein turnover in\nprimary cells","volume":"9","author":"Mathieson","year":"2018","journal-title":"Nat. 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Cancer\nRes."},{"key":"2026090210011631100_cit35","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1006\/geno.1998.5629","article-title":"The mouse\nmitotic checkpoint gene bub1b, a novel bub1 family member, is expressed\nin a cell cycle-dependent manner","volume":"55","author":"Davenport","year":"1999","journal-title":"Genomics"},{"key":"2026090210011631100_cit36","doi-asserted-by":"publisher","first-page":"2211","DOI":"10.2147\/ott.s101994","article-title":"Overexpression\nof BUB1B contributes to progression\nof prostate cancer and predicts poor outcome in patients with prostate\ncancer","volume":"9","author":"Zhong","year":"2016","journal-title":"OncoTargets Ther."},{"key":"2026090210011631100_cit37","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1126\/science.aaf7865","article-title":"Chemical genetic discovery of PARP targets reveals\na role for PARP-1 in transcription elongation","volume":"353","author":"Gibson","year":"2016","journal-title":"Science"},{"key":"2026090210011631100_cit38","doi-asserted-by":"publisher","first-page":"3075","DOI":"10.1016\/j.celrep.2016.08.031","article-title":"SUMO Signaling\nby Hypoxic Inactivation\nof SUMO-Specific Isopeptidases","volume":"16","author":"Kunz","year":"2016","journal-title":"Cell Rep."},{"key":"2026090210011631100_cit39","doi-asserted-by":"publisher","first-page":"1583","DOI":"10.1016\/j.celrep.2014.07.036","article-title":"Ultradeep human phosphoproteome reveals a distinct\nregulatory nature of Tyr and Ser\/Thr-based signaling","volume":"8","author":"Sharma","year":"2014","journal-title":"Cell Rep."},{"key":"2026090210011631100_cit40","doi-asserted-by":"publisher","first-page":"3069","DOI":"10.1128\/jvi.01875-08","article-title":"Ebola virus protein VP35 impairs\nthe function of interferon regulatory factor-activating kinases IKKepsilon\nand TBK-1","volume":"83","author":"Prins","year":"2009","journal-title":"J. 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