{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T02:56:44Z","timestamp":1790996204192,"version":"4.1.0"},"reference-count":55,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,5,12]],"date-time":"2021-05-12T00:00:00Z","timestamp":1620777600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["18-74-10095"],"award-info":[{"award-number":["18-74-10095"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Proteasomes are intracellular structures responsible for protein degradation. The 20S proteasome is a core catalytic element of the proteasome assembly. Variations of catalytic subunits generate different forms of 20S proteasomes including immunoproteasomes (iPs), which are present mostly in the immune cells. Certain cells of the immune system are primary targets of retroviruses. It has been shown that several viral proteins directly affect proteasome functionality, while inhibition of proteasome activity with broad specificity proteasome inhibitors stimulates viral transduction. Here we specifically addressed the role of the immunoproteasomes during early stages of viral transduction and investigated the effects of specific immunoproteasome inhibition and activation prior to infection using a panel of cell lines. Inhibition of iPs in hematopoietic cells with immunoproteasome-specific inhibitor ONX-0914 resulted in increased infection by VSV-G pseudotyped lentiviruses. Moreover, a tendency for increased infection of cloned cells with endogenously decreased proteasome activity was revealed. Conversely, activation of iPs by IFN-\u03b3 markedly reduced the viral infectivity, which was rescued upon simultaneous immunoproteasome inhibition. Our results indicate that immunoproteasome activity might be determinative for the cellular antiretroviral resistance at least for the cells with high iP content. Finally, therapeutic application of immunoproteasome inhibitors might promote retroviral infection of cells in vivo.<\/jats:p>","DOI":"10.3390\/cells10051185","type":"journal-article","created":{"date-parts":[[2021,5,12]],"date-time":"2021-05-12T10:59:12Z","timestamp":1620817152000},"page":"1185","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Immunoproteasome Activity and Content Determine Hematopoietic Cell Sensitivity to ONX-0914 and to the Infection of Cells with Lentiviruses"],"prefix":"10.3390","volume":"10","author":[{"given":"Elmira","family":"Vagapova","sequence":"first","affiliation":[{"name":"Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov Street 32, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3208-0485","authenticated-orcid":false,"given":"Alexander","family":"Burov","sequence":"additional","affiliation":[{"name":"Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov Street 32, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daria","family":"Spasskaya","sequence":"additional","affiliation":[{"name":"Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov Street 32, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5966-0914","authenticated-orcid":false,"given":"Timofey","family":"Lebedev","sequence":"additional","affiliation":[{"name":"Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov Street 32, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana","family":"Astakhova","sequence":"additional","affiliation":[{"name":"Koltzov Institute of Developmental Biology, Russian Academy of Sciences, Vavilov Street 26, 119334 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0610-5079","authenticated-orcid":false,"given":"Pavel","family":"Spirin","sequence":"additional","affiliation":[{"name":"Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov Street 32, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir","family":"Prassolov","sequence":"additional","affiliation":[{"name":"Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov Street 32, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vadim","family":"Karpov","sequence":"additional","affiliation":[{"name":"Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov Street 32, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4310-8073","authenticated-orcid":false,"given":"Alexey","family":"Morozov","sequence":"additional","affiliation":[{"name":"Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov Street 32, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e147","DOI":"10.1038\/emm.2014.117","article-title":"Degradation of misfolded proteins in neurodegenerative diseases: Therapeutic targets and strategies","volume":"47","author":"Ciechanover","year":"2015","journal-title":"Exp. Mol. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"22260","DOI":"10.1074\/jbc.M112360200","article-title":"Binding of Hydrophobic Peptides to Several Non-catalytic Sites Promotes Peptide Hydrolysis by All Active Sites of 20 S Proteasomes","volume":"277","author":"Kisselev","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/B978-0-12-397863-9.00003-1","article-title":"Immunoproteasomes: Structure, function, and antigen presentation","volume":"109","author":"Ferrington","year":"2012","journal-title":"Prog. Mol. Biol. Transl. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3508","DOI":"10.1002\/eji.201444902","article-title":"Proteasome isoforms exhibit only quantitative differences in cleavage and epitope generation","volume":"44","author":"Mishto","year":"2014","journal-title":"Eur. J. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"761","DOI":"10.3389\/fonc.2019.00761","article-title":"Proteasomes and Several Aspects of Their Heterogeneity Relevant to Cancer","volume":"9","author":"Morozov","year":"2019","journal-title":"Front. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"18599","DOI":"10.1073\/pnas.1009778107","article-title":"Two abundant proteasome subtypes that uniquely process some antigens presented by HLA class I molecules","volume":"107","author":"Guillaume","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2738","DOI":"10.3389\/fmicb.2018.02738","article-title":"Proteasomal Degradation Machinery: Favorite Target of HIV-1 Proteins","volume":"9","author":"Lata","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3845","DOI":"10.1128\/JVI.72.5.3845-3850.1998","article-title":"Antiviral Activity of the Proteasome on Incoming Human Immunodeficiency Virus Type 1","volume":"72","author":"Schwartz","year":"1998","journal-title":"J. Virol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"13057","DOI":"10.1073\/pnas.97.24.13057","article-title":"Proteasome inhibition interferes with Gag polyprotein processing, release, and maturation of HIV-1 and HIV-2","volume":"97","author":"Schubert","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1128\/JVI.79.1.644-648.2005","article-title":"The Ubiquitin-Proteasome System Facilitates the Transfer of Murine Coronavirus from Endosome to Cytoplasm during Virus Entry","volume":"79","author":"Yu","year":"2005","journal-title":"J. Virol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"7465","DOI":"10.1073\/pnas.0510483103","article-title":"Proteasome inhibitors uncouple rhesus TRIM5 restriction of HIV-1 reverse transcription and infection","volume":"103","author":"Wu","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3381","DOI":"10.1128\/JVI.02296-07","article-title":"Cellular Proteasome Activity Facilitates Herpes Simplex Virus Entry at a Postpenetration Step","volume":"82","author":"Delboy","year":"2008","journal-title":"J. Virol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"9625","DOI":"10.1128\/JVI.01048-10","article-title":"Inhibition of the Ubiquitin-Proteasome System Affects Influenza A Virus Infection at a Postfusion Step","volume":"84","author":"Widjaja","year":"2010","journal-title":"J. Virol."},{"key":"ref_14","first-page":"e01809-17","article-title":"The Ubiquitin-Proteasome System Is Necessary for Efficient Replication of Human Astrovirus","volume":"92","author":"Arias","year":"2017","journal-title":"J. Virol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.coviro.2015.09.005","article-title":"Interplay between the virus and the ubiquitin\u2013proteasome system: Molecular mechanism of viral pathogenesis","volume":"17","author":"Luo","year":"2016","journal-title":"Curr. Opin. Virol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Longhitano, L., Tibullo, D., Giallongo, C., Lazzarino, G., Tartaglia, N., Galimberti, S., Volti, G.L., Palumbo, G.A., and Liso, A. (2020). Proteasome Inhibitors as a Possible Therapy for SARS-CoV-2. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21103622"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"21","DOI":"10.3389\/fmicb.2015.00021","article-title":"The immunoproteasome and viral infection: A complex regulator of inflammation","volume":"6","author":"McCarthy","year":"2015","journal-title":"Front. Microbiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1134\/S0026893319040071","article-title":"Dynamics of the Functional Activity and Expression of Proteasome Subunits during Cellular Adaptation to Heat Shock","volume":"53","author":"Morozov","year":"2019","journal-title":"Mol. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1038\/mt.2008.6","article-title":"A Multicolor Panel of Novel Lentiviral \u201cGene Ontology\u201d (LeGO) Vectors for Functional Gene Analysis","volume":"16","author":"Weber","year":"2008","journal-title":"Mol. Ther."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1252","DOI":"10.1128\/JVI.76.3.1488-1495.2002","article-title":"Oncoretrovirus and Lentivirus Vectors Pseudotyped with Lymphocytic Choriomeningitis Virus Glycoprotein: Generation, Concentration, and Broad Host Range","volume":"76","author":"Beyer","year":"2002","journal-title":"J. Virol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"8463","DOI":"10.1128\/JVI.72.11.8463-8471.1998","article-title":"A Third-Generation Lentivirus Vector with a Conditional Packaging System","volume":"72","author":"Dull","year":"1998","journal-title":"J. Virol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1742-6405-10-1","article-title":"A new system for parallel drug screening against multiple-resistant HIV mutants based on lentiviral self-inactivating (SIN) vectors and multi-colour analyses","volume":"10","author":"Prokofjeva","year":"2013","journal-title":"AIDS Res. Ther."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1007\/s12192-017-0792-y","article-title":"Interplay between recombinant Hsp70 and proteasomes: Proteasome activity modulation and ubiquitin-independent cleavage of Hsp70","volume":"22","author":"Morozov","year":"2017","journal-title":"Cell Stress Chaperon"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1007\/978-1-61779-364-6_13","article-title":"Fluorescence-Based Proteasome Activity Profiling","volume":"803","author":"Schuurman","year":"2012","journal-title":"Methods Mol. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3027","DOI":"10.1021\/pr500193k","article-title":"Label-Free Quantitative Proteomics Reveals the Dynamics of Proteasome Complexes Composition and Stoichiometry in a Wide Range of Human Cell Lines","volume":"13","author":"Fabre","year":"2014","journal-title":"J. Proteome Res."},{"key":"ref_26","first-page":"119","article-title":"The major-histocompatibility-complex-encoded beta-type proteasome subunits LMP2 and LMP7. Evidence that LMP2 and LMP7 are synthesized as proproteins and that cellular levels of both mRNA and LMP-containing 20S proteasomes are differentially regulated","volume":"216","author":"Frentzel","year":"1993","journal-title":"JBIC J. Biol. Inorg. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"34019","DOI":"10.1038\/srep34019","article-title":"Expression of immunoproteasome genes is regulated by cell-intrinsic and -extrinsic factors in human cancers","volume":"6","author":"Rouette","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_28","first-page":"4199","article-title":"A Set of Activity-Based Probes to Visualize Human (Immuno)proteasome Activities","volume":"55","author":"Xin","year":"2015","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-018-03432-4","article-title":"Structural basis for the recognition of LDL-receptor family members by VSV glycoprotein","volume":"9","author":"Nikolic","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1093\/oxfordjournals.jbchem.a124327","article-title":"Interferon-gamma induces different subunit organizations and functional diversity of proteasomes","volume":"115","author":"Aki","year":"1994","journal-title":"J. Biochem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1165\/ajrcmb.27.2.4792","article-title":"Proteasome Inhibitors Stimulate Interleukin-8 Expression via Ras and Apoptosis Signal-Regulating Kinase-dependent Extracellular Signal-Related Kinase and c-Jun N-Terminal Kinase Activation","volume":"27","author":"Wu","year":"2002","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.1053\/jhep.2003.50470","article-title":"Inhibition of proteasome function leads to NF-\u03baB-independent IL-8 expression in human hepatocytes","volume":"38","author":"Barve","year":"2003","journal-title":"Hepatology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2837","DOI":"10.4049\/jimmunol.1300895","article-title":"Proteasome Inhibition by Bortezomib Increases IL-8 Expression in Androgen-Independent Prostate Cancer Cells: The Role of IKK\u03b1","volume":"191","author":"Manna","year":"2013","journal-title":"J. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1146\/annurev.genom.7.080505.115700","article-title":"The Evolutionary Dynamics of Human Endogenous Retroviral Families","volume":"7","author":"Bannert","year":"2006","journal-title":"Annu. Rev. Genom. Hum. Genet."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12913-018-3568-x","article-title":"Global research output on HIV\/AIDS\u2013related medication adherence from 1980 to 2017","volume":"18","author":"Sweileh","year":"2018","journal-title":"BMC Health Serv. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1038\/nrmicro3449","article-title":"HIV-1 and interferons: Who\u2019s interfering with whom?","volume":"13","author":"Doyle","year":"2015","journal-title":"Nat. Rev. Genet."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-019-08810-0","article-title":"Cellular TRIM33 restrains HIV-1 infection by targeting viral integrase for proteasomal degradation","volume":"10","author":"Ali","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1502","DOI":"10.1038\/nm.3956","article-title":"MARCH8 inhibits HIV-1 infection by reducing virion incorporation of envelope glycoproteins","volume":"21","author":"Tada","year":"2015","journal-title":"Nat. Med."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Seissler, T., Marquet, R., and Paillart, J.-C. (2017). Hijacking of the Ubiquitin\/Proteasome Pathway by the HIV Auxiliary Proteins. Viruses, 9.","DOI":"10.3390\/v9110322"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1126\/science.1089591","article-title":"Induction of APOBEC3G Ubiquitination and Degradation by an HIV-1 Vif-Cul5-SCF Complex","volume":"302","author":"Yu","year":"2003","journal-title":"Science"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1128\/JVI.01795-10","article-title":"Serine-Threonine Ubiquitination Mediates Downregulation of BST-2\/Tetherin and Relief of Restricted Virion Release by HIV-1 Vpu","volume":"85","author":"Tokarev","year":"2010","journal-title":"J. Virol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"12550","DOI":"10.1074\/jbc.M112.340711","article-title":"HIV\/Simian Immunodeficiency Virus (SIV) Accessory Virulence Factor Vpx Loads the Host Cell Restriction Factor SAMHD1 onto the E3 Ubiquitin Ligase Complex CRL4DCAF1","volume":"287","author":"Ahn","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"8145","DOI":"10.1074\/jbc.272.13.8145","article-title":"HIV-1 Tat Inhibits the 20 S Proteasome and Its 11 S Regulator-mediated Activation","volume":"272","author":"Seeger","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/S0014-5793(03)01025-1","article-title":"Human immunodeficiency virus-1 Tat protein interacts with distinct proteasomal \u03b1 and \u03b2 subunits","volume":"553","author":"Apcher","year":"2003","journal-title":"FEBS Lett."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"7049","DOI":"10.1128\/JVI.00327-09","article-title":"Human Immunodeficiency Virus Type 1 Gag p24 Alters the Composition of Immunoproteasomes and Affects Antigen Presentation","volume":"83","author":"Steers","year":"2009","journal-title":"J. Virol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.cellimm.2004.07.005","article-title":"Alcohol and HIV decrease proteasome and immunoproteasome function in macrophages: Implications for impaired immune function during disease","volume":"229","author":"Haorah","year":"2004","journal-title":"Cell. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1038\/s41564-019-0402-0","article-title":"Immunoproteasome activation enables human TRIM5\u03b1 restriction of HIV-1","volume":"4","author":"Apolonia","year":"2019","journal-title":"Nat. Microbiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"9754","DOI":"10.1128\/JVI.01052-06","article-title":"Proteasome Inhibition Reveals that a Functional Preintegration Complex Intermediate Can Be Generated during Restriction by Diverse TRIM5 Proteins","volume":"80","author":"Anderson","year":"2006","journal-title":"J. Virol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1038\/nm.1978","article-title":"A selective inhibitor of the immunoproteasome subunit LMP7 blocks cytokine production and attenuates progression of experimental arthritis","volume":"15","author":"Muchamuel","year":"2009","journal-title":"Nat. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e33","DOI":"10.4110\/in.2018.18.e33","article-title":"Direct Antiviral Mechanisms of Interferon-Gamma","volume":"18","author":"Kang","year":"2018","journal-title":"Immune Netw."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1186\/1742-4690-10-120","article-title":"Proteasome inhibitors act as bifunctional antagonists of human immunodeficiency virus type 1 latency and replication","volume":"10","author":"Miller","year":"2013","journal-title":"Retrovirology"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Uddin, M.M., Zou, Y., Sharma, T., Gatla, H.R., and Vancurova, I. (2018). Proteasome inhibition induces IKK-dependent interleukin-8 expression in triple negative breast cancer cells: Opportunity for combination therapy. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0201858"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2687","DOI":"10.1074\/jbc.M113.502641","article-title":"Proteasome Inhibition Increases Recruitment of I\u03baB Kinase \u03b2 (IKK\u03b2), S536P-p65, and Transcription Factor EGR1 to Interleukin-8 (IL-8) Promoter, Resulting in Increased IL-8 Production in Ovarian Cancer Cells","volume":"289","author":"Singha","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1183\/09031936.04.00079203","article-title":"Proteasome inhibitors modulate chemokine production in lung epithelial and monocytic cells","volume":"24","author":"Gerber","year":"2004","journal-title":"Eur. Respir. J."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.1002\/eji.201747458","article-title":"The immunoproteasome inhibitor ONX-0914 regulates inflammation and expression of contraction associated proteins in myometrium","volume":"48","author":"Liong","year":"2018","journal-title":"Eur. J. Immunol."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/5\/1185\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:59:53Z","timestamp":1760162393000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/5\/1185"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,12]]},"references-count":55,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2021,5]]}},"alternative-id":["cells10051185"],"URL":"https:\/\/doi.org\/10.3390\/cells10051185","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,12]]}}}