{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T16:09:23Z","timestamp":1790438963103,"version":"4.1.0"},"reference-count":62,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2020,8,19]],"date-time":"2020-08-19T00:00:00Z","timestamp":1597795200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI131586"],"award-info":[{"award-number":["AI131586"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Mammarenaviruses include several known human pathogens, such as the prototypic lymphocytic choriomeningitis virus (LCMV) that can cause neurological diseases and Lassa virus (LASV) that causes endemic hemorrhagic fever infection. LASV-infected patients show diverse clinical manifestations ranging from asymptomatic infection to hemorrhage, multi-organ failures and death, the mechanisms of which have not been well characterized. We have previously shown that the matrix protein Z of pathogenic arenaviruses, including LASV and LCMV, can strongly inhibit the ability of the innate immune protein RIG-I to suppress type I interferon (IFN-I) expression, which serves as a mechanism of viral immune evasion and virulence. Here, we show that Z proteins of diverse LASV isolates derived from rodents and humans have a high degree of sequence variations at their N- and C-terminal regions and produce variable degrees of inhibition of human RIG-I (hRIG-I) function in an established IFN-\u03b2 promoter-driven luciferase (LUC) reporter assay. Additionally, we show that Z proteins of four known LCMV strains can also inhibit hRIG-I at variable degrees of efficiency. Collectively, our results confirm that Z proteins of pathogenic LASV and LCMV can inhibit hRIG-I and suggest that strain variations of the Z proteins can influence their efficiency to suppress host innate immunity that might contribute to viral virulence and disease heterogeneity.<\/jats:p>","DOI":"10.3390\/v12090907","type":"journal-article","created":{"date-parts":[[2020,8,19]],"date-time":"2020-08-19T09:22:31Z","timestamp":1597828951000},"page":"907","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Effect of Strain Variations on Lassa Virus Z Protein-Mediated Human RIG-I Inhibition"],"prefix":"10.3390","volume":"12","author":[{"given":"Qinfeng","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, St Paul, MN 55108, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoying","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, St Paul, MN 55108, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7040-4495","authenticated-orcid":false,"given":"Morgan","family":"Brisse","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, St Paul, MN 55108, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hinh","family":"Ly","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, St Paul, MN 55108, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6002-6868","authenticated-orcid":false,"given":"Yuying","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, St Paul, MN 55108, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1093\/infdis\/155.3.456","article-title":"Clinical Virology of Lassa Fever in Hospitalized Patients","volume":"155","author":"Johnson","year":"1987","journal-title":"J. Infect. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1093\/infdis\/155.3.437","article-title":"A Prospective Study of the Epidemiology and Ecology of Lassa Fever","volume":"155","author":"McCormick","year":"1987","journal-title":"J. Infect. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"25280","DOI":"10.1038\/srep25280","article-title":"New Hosts of The Lassa Virus","volume":"6","author":"Olayemi","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1186\/s13071-018-2991-5","article-title":"Widespread arenavirus occurrence and seroprevalence in small mammals, Nigeria","volume":"11","author":"Olayemi","year":"2018","journal-title":"Parasites Vectors"},{"key":"ref_5","first-page":"75","article-title":"Lassa Fever","volume":"262","author":"McCormick","year":"2002","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1093\/infdis\/155.3.445","article-title":"A Case-Control Study of the Clinical Diagnosis and Course of Lassa Fever","volume":"155","author":"McCormick","year":"1987","journal-title":"J. Infect. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1136\/bmj.311.7009.857","article-title":"Review of cases of nosocomial Lassa fever in Nigeria: The high price of poor medical practice","volume":"311","author":"Tomori","year":"1995","journal-title":"BMJ"},{"key":"ref_8","unstructured":"(2020, June 19). WHO Lassa Fever\u2014Nigeria, Disease Outbreak News. Available online: https:\/\/www.who.int\/csr\/don\/14-february-2019-lassa-fever-nigeria\/en\/."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"6992","DOI":"10.1128\/JVI.74.15.6992-7004.2000","article-title":"Genetic Diversity among Lassa Virus Strains","volume":"74","author":"Bowen","year":"2000","journal-title":"J. Virol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1016\/j.cell.2015.07.020","article-title":"Clinical Sequencing Uncovers Origins and Evolution of Lassa Virus","volume":"162","author":"Andersen","year":"2015","journal-title":"Cell"},{"key":"ref_11","unstructured":"Knipe, D.M., and Howley, P.M. (2013). Arenaviridae. Fields Virology, Lippincott Williams & Wilkins. [5th ed.]."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"283","DOI":"10.3390\/pathogens4020283","article-title":"Human Hemorrhagic Fever Causing Arenaviruses: Molecular Mechanisms Contributing to Virus Virulence and Disease Pathogenesis","volume":"4","author":"Shao","year":"2015","journal-title":"Pathogens"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"372","DOI":"10.3389\/fimmu.2019.00372","article-title":"Hemorrhagic Fever-Causing Arenaviruses: Lethal Pathogens and Potent Immune Suppressors","volume":"10","author":"Brisse","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.antiviral.2012.12.003","article-title":"Targeting virulence mechanisms for the prevention and therapy of arenaviral hemorrhagic fever","volume":"97","author":"McLay","year":"2013","journal-title":"Antivir. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1038\/nature09605","article-title":"Cap binding and immune evasion revealed by Lassa nucleoprotein structure","volume":"468","author":"Qi","year":"2010","journal-title":"Nature"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2396","DOI":"10.1073\/pnas.1016404108","article-title":"Structure of the Lassa virus nucleoprotein reveals a dsRNA-specific 3\u2032 to 5\u2032 exonuclease activity essential for immune suppression","volume":"108","author":"Hastie","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3810","DOI":"10.1128\/JVI.03049-15","article-title":"Inhibition of Innate Immune Responses Is Key to Pathogenesis by Arenaviruses","volume":"90","author":"Meyer","year":"2016","journal-title":"J. Virol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"6161","DOI":"10.1128\/JVI.00738-15","article-title":"Correction for Xing et al., The Z Proteins of Pathogenic but Not Nonpathogenic Arenaviruses Inhibit RIG-i-Like Receptor-Dependent Interferon Production","volume":"89","author":"Xing","year":"2015","journal-title":"J. Virol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Sattler, R.A., Paessler, S., Ly, H., and Huang, C. (2020). Animal Models of Lassa Fever. Pathogens, 9.","DOI":"10.3390\/pathogens9030197"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1016\/0035-9203(85)90386-4","article-title":"Endemic Lassa fever in Liberia. III. Characterization of Lassa virus isolates","volume":"79","author":"Jahrling","year":"1985","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2920","DOI":"10.1128\/JVI.02948-15","article-title":"Animal Model of Sensorineural Hearing Loss Associated with Lassa Virus Infection","volume":"90","author":"Yun","year":"2015","journal-title":"J. Virol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1316","DOI":"10.1093\/infdis\/jit004","article-title":"A Recently Isolated Lassa Virus from Mali Demonstrates Atypical Clinical Disease Manifestations and Decreased Virulence in Cynomolgus Macaques","volume":"207","author":"Safronetz","year":"2013","journal-title":"J. Infect. Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"9794","DOI":"10.1128\/JVI.00385-12","article-title":"Biological Roles and Functional Mechanisms of Arenavirus Z Protein in Viral Replication","volume":"86","author":"Wang","year":"2012","journal-title":"J. Virol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1006\/viro.1997.8722","article-title":"Completion of the Lassa fever virus sequence and identification of a RING finger open reading frame at the L RNA 5\u2032 End","volume":"235","author":"Djavani","year":"1997","journal-title":"Virology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.virol.2003.09.009","article-title":"Sequence analysis of L RNA of Lassa virus","volume":"318","author":"Vieth","year":"2004","journal-title":"Virology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1128\/JCM.01891-10","article-title":"Current Molecular Epidemiology of Lassa Virus in Nigeria","volume":"49","author":"Ehichioya","year":"2010","journal-title":"J. Clin. Microbiol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Safronetz, D., Sogoba, N., L\u00f3pez, J.E., Ma\u00efga, O., Dahlstrom, E., Zivcec, M., Feldmann, F., Haddock, E., Fischer, R.J., and Anderson, J.M. (2013). Geographic Distribution and Genetic Characterization of Lassa Virus in Sub-Saharan Mali. PLoS Negl. Trop. Dis., 7.","DOI":"10.1371\/journal.pntd.0002582"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"6595","DOI":"10.1128\/JVI.00009-15","article-title":"In vitro and in vivo characterizations of the Pichinde viral NP exoribonuclease function","volume":"89","author":"Huang","year":"2015","journal-title":"J. Virol."},{"key":"ref_29","first-page":"315","article-title":"Arenavirus Diversity and Evolution: Quasispecies In Vivo","volume":"299","author":"Sevilla","year":"2006","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref_30","first-page":"231","article-title":"Arenavirus Quasispecies and Their Biological Implications","volume":"392","author":"Martin","year":"2016","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.spen.2012.02.002","article-title":"Lymphocytic choriomeningitis virus: An underrecognized cause of neurologic disease in the fetus, child, and adult","volume":"19","author":"Bonthius","year":"2012","journal-title":"Semin. Pediatr. Neurol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Abdel-Hakeem, M.S. (2019). Viruses Teaching Immunology: Role of LCMV Model and Human Viral Infections in Immunological Discoveries. Viruses, 11.","DOI":"10.3390\/v11020106"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1719","DOI":"10.1084\/jem.167.5.1719","article-title":"Organ-specific selection of viral variants during chronic infection","volume":"167","author":"Ahmed","year":"1988","journal-title":"J. Exp. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1126\/science.81.2099.298","article-title":"A FILTERABLE VIRUS RECOVERED FROM WHITE MICE","volume":"81","author":"Traub","year":"1935","journal-title":"Science"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1538\/expanim.16-0097","article-title":"Difference of two new LCMV strains in lethality and viral genome load in tissues","volume":"66","author":"Takagi","year":"2017","journal-title":"Exp. Anim."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1126\/science.81.2105.439.b","article-title":"Meningitis in man caused by a filterable virus","volume":"81","author":"Rivers","year":"1935","journal-title":"Science"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1006\/viro.1999.9638","article-title":"Identification of MaTu-MX agent as a new strain of lymphocytic choriomeningitis virus (LCMV) and serological indication of horizontal spread of LCMV in human population","volume":"257","author":"Kaluz","year":"1999","journal-title":"Virology"},{"key":"ref_38","first-page":"272","article-title":"Lymphocytic choriomeningitis infection undetected by dirty-bedding sentinel monitoring and revealed after embryo transfer of an inbred strain derived from wild mice","volume":"57","author":"Ike","year":"2007","journal-title":"Comp. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.3201\/eid1607.091902","article-title":"High Diversity and Ancient Common Ancestry of Lymphocytic Choriomeningitis Virus","volume":"16","author":"Palacios","year":"2010","journal-title":"Emerg. Infect. Dis."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1099\/vir.0.83464-0","article-title":"Genomic and biological characterization of aggressive and docile strains of lymphocytic choriomeningitis virus rescued from a plasmid-based reverse-genetics system","volume":"89","author":"Chen","year":"2008","journal-title":"J. Gen. Virol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"134","DOI":"10.12688\/f1000research.16989.1","article-title":"Lassa virus diversity and feasibility for universal prophylactic vaccine","volume":"8","author":"Lukashevich","year":"2019","journal-title":"F1000Research"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"5173","DOI":"10.1111\/mec.14282","article-title":"Evolutionary analysis of Old World arenaviruses reveals a major adaptive contribution of the viral polymerase","volume":"26","author":"Pontremoli","year":"2017","journal-title":"Mol. Ecol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2973","DOI":"10.3390\/v4112973","article-title":"Multifunctional Nature of the Arenavirus RING Finger Protein Z","volume":"4","author":"Fehling","year":"2012","journal-title":"Viruses"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"9415","DOI":"10.1128\/JVI.75.19.9415-9426.2001","article-title":"RING Finger Z Protein of Lymphocytic Choriomeningitis Virus (LCMV) Inhibits Transcription and RNA Replication of an LCMV S-Segment Minigenome","volume":"75","author":"Cornu","year":"2001","journal-title":"J. Virol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"6678","DOI":"10.1128\/JVI.76.13.6678-6688.2002","article-title":"Characterization of the Arenavirus RING Finger Z Protein Regions Required for Z-Mediated Inhibition of Viral RNA Synthesis","volume":"76","author":"Cornu","year":"2002","journal-title":"J. Virol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"19743","DOI":"10.1073\/pnas.1112742108","article-title":"Arenavirus Z protein controls viral RNA synthesis by locking a polymerase-promoter complex","volume":"108","author":"Kranzusch","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"10383","DOI":"10.1128\/JVI.77.19.10383-10393.2003","article-title":"Tacaribe Virus Z Protein Interacts with the L Polymerase Protein to Inhibit Viral RNA Synthesis","volume":"77","author":"Wilda","year":"2003","journal-title":"J. Virol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"9451","DOI":"10.1128\/JVI.00499-07","article-title":"Arenavirus Z-Glycoprotein Association Requires Z Myristoylation but Not Functional RING or Late Domains","volume":"81","author":"Capul","year":"2007","journal-title":"J. Virol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.virusres.2003.11.017","article-title":"Characterization of the Lassa virus matrix protein Z: Electron microscopic study of virus-like particles and interaction with the nucleoprotein (NP)","volume":"100","author":"Eichler","year":"2004","journal-title":"Virus Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3178","DOI":"10.1128\/JVI.02240-09","article-title":"Viral Protein Determinants of Lassa Virus Entry and Release from Polarized Epithelial Cells","volume":"84","author":"Schlie","year":"2010","journal-title":"J. Virol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"7029","DOI":"10.1128\/JVI.00329-09","article-title":"The RING Domain and the L79 Residue of Z Protein Are Involved in both the Rescue of Nucleocapsids and the Incorporation of Glycoproteins into Infectious Chimeric Arenavirus-Like Particles","volume":"83","author":"Casabona","year":"2009","journal-title":"J. Virol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"10700","DOI":"10.1128\/JVI.77.19.10700-10705.2003","article-title":"Lassa virus Z protein is a matrix protein and sufficient for the release of virus-like particles [corrected]","volume":"77","author":"Strecker","year":"2003","journal-title":"J. Virol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"12978","DOI":"10.1073\/pnas.2133782100","article-title":"The small RING finger protein Z drives arenavirus budding: Implications for antiviral strategies","volume":"100","author":"Perez","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1128\/JVI.72.1.758-766.1998","article-title":"An Arenavirus RING (Zinc-Binding) Protein Binds the Oncoprotein Promyelocyte Leukemia Protein (PML) and Relocates PML Nuclear Bodies to the Cytoplasm","volume":"72","author":"Borden","year":"1998","journal-title":"J. Virol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3819","DOI":"10.1128\/JVI.72.5.3819-3826.1998","article-title":"Two RING Finger Proteins, the Oncoprotein PML and the Arenavirus Z Protein, Colocalize with the Nuclear Fraction of the Ribosomal P Proteins","volume":"72","author":"Borden","year":"1998","journal-title":"J. Virol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"3293","DOI":"10.1128\/JVI.74.7.3293-3300.2000","article-title":"The Lymphocytic Choriomeningitis Virus RING Protein Z Associates with Eukaryotic Initiation Factor 4E and Selectively Represses Translation in a RING-Dependent Manner","volume":"74","author":"Dwyer","year":"2000","journal-title":"J. Virol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1785","DOI":"10.1128\/JVI.01362-09","article-title":"Z Proteins of New World Arenaviruses Bind RIG-I and Interfere with Type I Interferon Induction","volume":"84","author":"Fan","year":"2009","journal-title":"J. Virol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1802","DOI":"10.3390\/v4091802","article-title":"Animal Models, Prophylaxis, and Therapeutics for Arenavirus Infections","volume":"4","author":"Vela","year":"2012","journal-title":"Viruses"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"9192","DOI":"10.1128\/JVI.00555-06","article-title":"Inhibition of the Type I Interferon Response by the Nucleoprotein of the Prototypic Arenavirus Lymphocytic Choriomeningitis Virus","volume":"80","author":"Rosario","year":"2006","journal-title":"J. Virol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"12093","DOI":"10.1128\/JVI.00429-11","article-title":"Lassa Virus Nucleoprotein Mutants Generated by Reverse Genetics Induce a Robust Type I Interferon Response in Human Dendritic Cells and Macrophages","volume":"85","author":"Carnec","year":"2011","journal-title":"J. Virol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"7079","DOI":"10.1128\/JVI.00526-15","article-title":"Highly Pathogenic New World and Old World Human Arenaviruses Induce Distinct Interferon Responses in Human Cells","volume":"89","author":"Huang","year":"2015","journal-title":"J. Virol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"16949","DOI":"10.1074\/jbc.M112.420521","article-title":"Structures of Arenaviral Nucleoproteins with Triphosphate dsRNA Reveal a Unique Mechanism of Immune Suppression","volume":"288","author":"Jiang","year":"2013","journal-title":"J. Biol. Chem."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/12\/9\/907\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:02:53Z","timestamp":1760176973000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/12\/9\/907"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,19]]},"references-count":62,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2020,9]]}},"alternative-id":["v12090907"],"URL":"https:\/\/doi.org\/10.3390\/v12090907","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,19]]}}}