{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T21:51:43Z","timestamp":1790459503898,"version":"4.1.0"},"reference-count":29,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2020,8,7]],"date-time":"2020-08-07T00:00:00Z","timestamp":1596758400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Reactivation of BK polyomavirus (BKPyV) infection is frequently increasing in transplant recipients treated with potent immunosuppressants and highlights the importance of immune system components in controlling viral reactivation. However, the immune response to BKPyV in general and the role of antiviral cytokines in infection control in particular are poorly understood. Here, we investigated the efficacy of interferons (IFN) alpha, lambda and gamma with regard to the BKPyV multiplication in Vero cells. Treatment with IFN-gamma inhibited the expression of the viral protein VP1 in a dose-dependent manner and decreased the expression of early and late viral transcripts. Viral inhibition by IFN-gamma was confirmed in human cells (Caki-1 cells and renal proximal tubular epithelial cells). One of the IFN-stimulated genes most strongly induced by IFN-gamma was the coding for the enzyme indoleamine 2,3 dioxygenase (IDO), which is known to limit viral replication and regulates the host immune system. The antiviral activity induced by IFN-gamma could be reversed by the addition of an IDO inhibitor, indicating that IDO has a specific role in anti-BKPyV activity. A better understanding of the action mechanism of these IFN-gamma-induced antiviral proteins might facilitate the development of novel therapeutic strategies.<\/jats:p>","DOI":"10.3390\/v12080865","type":"journal-article","created":{"date-parts":[[2020,8,10]],"date-time":"2020-08-10T05:07:23Z","timestamp":1597036043000},"page":"865","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Indoleamine 2,3-Dioxygenase Is Involved in Interferon Gamma\u2019s Anti-BKPyV Activity in Renal Cells"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2209-0660","authenticated-orcid":false,"given":"Tony","family":"Fiore","sequence":"first","affiliation":[{"name":"UR4294, Infectious Agents, Resistance and Chemotherapy, University Health Research Center, University of Picardie Jules Verne, F-80054 Amiens, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2991-6365","authenticated-orcid":false,"given":"Elodie","family":"Martin","sequence":"additional","affiliation":[{"name":"UR4294, Infectious Agents, Resistance and Chemotherapy, University Health Research Center, University of Picardie Jules Verne, F-80054 Amiens, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00e9ronique","family":"Descamps","sequence":"additional","affiliation":[{"name":"UR4294, Infectious Agents, Resistance and Chemotherapy, University Health Research Center, University of Picardie Jules Verne, F-80054 Amiens, France"},{"name":"Department of Virology, Amiens University Hospital, F-80000 Amiens, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Etienne","family":"Brochot","sequence":"additional","affiliation":[{"name":"UR4294, Infectious Agents, Resistance and Chemotherapy, University Health Research Center, University of Picardie Jules Verne, F-80054 Amiens, France"},{"name":"Department of Virology, Amiens University Hospital, F-80000 Amiens, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginie","family":"Morel","sequence":"additional","affiliation":[{"name":"UR4294, Infectious Agents, Resistance and Chemotherapy, University Health Research Center, University of Picardie Jules Verne, F-80054 Amiens, France"},{"name":"Department of Virology, Amiens University Hospital, F-80000 Amiens, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynda","family":"Handala","sequence":"additional","affiliation":[{"name":"UR4294, Infectious Agents, Resistance and Chemotherapy, University Health Research Center, University of Picardie Jules Verne, F-80054 Amiens, France"},{"name":"Department of Virology, Amiens University Hospital, F-80000 Amiens, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatima","family":"Dakroub","sequence":"additional","affiliation":[{"name":"UR4294, Infectious Agents, Resistance and Chemotherapy, University Health Research Center, University of Picardie Jules Verne, F-80054 Amiens, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2670-3148","authenticated-orcid":false,"given":"Sandrine","family":"Castelain","sequence":"additional","affiliation":[{"name":"UR4294, Infectious Agents, Resistance and Chemotherapy, University Health Research Center, University of Picardie Jules Verne, F-80054 Amiens, France"},{"name":"Department of Virology, Amiens University Hospital, F-80000 Amiens, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilles","family":"Duverlie","sequence":"additional","affiliation":[{"name":"UR4294, Infectious Agents, Resistance and Chemotherapy, University Health Research Center, University of Picardie Jules Verne, F-80054 Amiens, France"},{"name":"Department of Virology, Amiens University Hospital, F-80000 Amiens, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6884-2456","authenticated-orcid":false,"given":"Fran\u00e7ois","family":"Helle","sequence":"additional","affiliation":[{"name":"UR4294, Infectious Agents, Resistance and Chemotherapy, University Health Research Center, University of Picardie Jules Verne, F-80054 Amiens, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Fran\u00e7ois","sequence":"additional","affiliation":[{"name":"UR4294, Infectious Agents, Resistance and Chemotherapy, University Health Research Center, University of Picardie Jules Verne, F-80054 Amiens, France"},{"name":"Department of Virology, Amiens University Hospital, F-80000 Amiens, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/0272-6386(95)90608-8","article-title":"BK virus infection in a kidney allograft diagnosed by needle biopsy","volume":"26","author":"Purighalla","year":"1995","journal-title":"Am. J. Kidney Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1097\/00007890-199903270-00022","article-title":"Polyomavirus disease under new immunosuppressive drugs: A cause of renal graft dysfunction and graft loss","volume":"67","author":"Binet","year":"1999","journal-title":"Transplantation"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e13528","DOI":"10.1111\/ctr.13528","article-title":"AST infectious diseases community of practice BK polyomavirus in solid organ transplantation\u2014Guidelines from the American society of transplantation infectious diseases community of practice","volume":"33","author":"Hirsch","year":"2019","journal-title":"Clin. Transplant."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1097\/00007890-199901150-00018","article-title":"Human Polyoma virus-associated interstitial nephritis in the allograft kidney","volume":"67","author":"Randhawa","year":"1999","journal-title":"Transplantation"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1089\/jir.1987.7.429","article-title":"Virus interference. I. The interferon","volume":"7","author":"Isaacs","year":"1987","journal-title":"J. Interferon Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1128\/JVI.01571-06","article-title":"Inhibitory effect of gamma interferon on BK virus gene expression and replication","volume":"81","author":"Abend","year":"2007","journal-title":"J. Virol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1038\/nri1457","article-title":"Ido expression by dendritic cells: Tolerance and tryptophan catabolism","volume":"4","author":"Mellor","year":"2004","journal-title":"Nat. Rev. Immunol."},{"key":"ref_8","first-page":"957","article-title":"Role of IFN-gamma-induced indoleamine 2,3 dioxygenase and inducible nitric oxide synthase in the replication of human cytomegalovirus in retinal pigment epithelial cells","volume":"162","author":"Bodaghi","year":"1999","journal-title":"J. Immunol. Baltim. Md 1950"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2632","DOI":"10.1128\/JVI.78.5.2632-2636.2004","article-title":"Role of indoleamine-2,3-dioxygenase in alpha\/beta and gamma interferon-mediated antiviral effects against herpes simplex virus infections","volume":"78","author":"Adams","year":"2004","journal-title":"J. Virol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"7768","DOI":"10.1128\/JVI.79.12.7768-7776.2005","article-title":"Indoleamine 2,3-dioxygenase mediates cell type-specific anti-measles virus activity of gamma interferon","volume":"79","author":"Obojes","year":"2005","journal-title":"J. Virol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1089\/vim.2005.18.722","article-title":"Role of indoleamine 2,3-dioxygenase in antiviral activity of interferon-gamma against vaccinia virus","volume":"18","author":"Terajima","year":"2005","journal-title":"Viral Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"11798","DOI":"10.1128\/JVI.01316-07","article-title":"Identification of amino acid residues in BK virus VP1 that are critical for viability and growth","volume":"81","author":"Dugan","year":"2007","journal-title":"J. Virol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e01834-19","DOI":"10.1128\/JVI.01834-19","article-title":"BK polyomavirus hijacks extracellular vesicles for En Bloc transmission","volume":"94","author":"Handala","year":"2020","journal-title":"J. Virol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.antiviral.2015.03.012","article-title":"The kinase-inhibitor sorafenib inhibits multiple steps of the hepatitis C virus infectious cycle in vitro","volume":"118","author":"Descamps","year":"2015","journal-title":"Antivir. Res."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Handala, L., Fiore, T., and Rouill, Y. (2019). QuantIF: An Imagej macro to automatically determine the percentage of infected cells after immunofluorescence. Viruses, 11.","DOI":"10.3390\/v11020165"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1186\/1743-422X-6-70","article-title":"Enhanced anti-HCV activity of interferon alpha 17 subtype","volume":"6","author":"Dubois","year":"2009","journal-title":"Virol. J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1159\/000375161","article-title":"Antiviral and immunoregulatory effects of indoleamine-2,3-dioxygenase in hepatitis C virus infection","volume":"7","author":"Lepiller","year":"2015","journal-title":"J. Innate Immun."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1189\/jlb.1011532","article-title":"Flavivirus infection induces indoleamine 2,3-dioxygenase in human monocyte-derived macrophages via tumor necrosis factor and NF-\u03baB","volume":"91","author":"Yeung","year":"2012","journal-title":"J. Leukoc. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.1128\/JVI.01998-10","article-title":"Indoleamine 2,3-dioxygenase mediates the antiviral effect of gamma interferon against hepatitis B virus in human hepatocyte-derived cells","volume":"85","author":"Mao","year":"2011","journal-title":"J. Virol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1016\/j.micinf.2004.04.007","article-title":"Inhibition of human herpes simplex virus type 2 by interferon gamma and tumor necrosis factor alpha is mediated by indoleamine 2,3-dioxygenase","volume":"6","author":"Adams","year":"2004","journal-title":"Microbes Infect."},{"key":"ref_21","unstructured":"(2020, May 12). Interferon Gamma Prevents Infectious Entry of Human Papillomavirus 16 via an L2-Dependent Mechanism, Available online: https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC5411602\/."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e00903-16","DOI":"10.1128\/mBio.00903-16","article-title":"JC polyomavirus infection of primary human renal epithelial cells is controlled by a type I IFN-induced response","volume":"7","author":"Assetta","year":"2016","journal-title":"mBio"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1888","DOI":"10.1128\/MCB.26.5.1888-1897.2006","article-title":"Inquiring into the differential action of interferons (IFNs): An IFN-\u03b12 mutant with enhanced affinity to IFNAR1 is functionally similar to IFN-\u03b2","volume":"26","author":"Jaitin","year":"2006","journal-title":"Mol. Cell. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2443","DOI":"10.1111\/j.1600-6143.2011.03693.x","article-title":"BK virus-specific immunity kinetics: A predictor of recovery from polyomavirus BK-associated nephropathy","volume":"11","author":"Schachtner","year":"2011","journal-title":"Am. J. Transplant."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2159","DOI":"10.1111\/ajt.13252","article-title":"The loss of BKV-specific immunity from pretransplantation to posttransplantation identifies kidney transplant recipients at increased risk of BKV replication","volume":"15","author":"Schachtner","year":"2015","journal-title":"Am. J. Transplant."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Bae, H., Na, D.H., Chang, J.-Y., Park, K.H., Min, J.W., Ko, E.J., Lee, H., Yang, C.W., Chung, B.H., and Oh, E.-J. (2020). Usefulness of BK virus-specific interferon-\u03b3 enzyme-linked immunospot assay for predicting the outcome of BK virus infection in kidney transplant recipients. Korean J. Intern. Med.","DOI":"10.3904\/kjim.2019.339"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.trim.2015.05.003","article-title":"IDO expressing dendritic cells suppress allograft rejection of small bowel transplantation in mice by expansion of Foxp3+ regulatory T cells","volume":"33","author":"Xie","year":"2015","journal-title":"Transpl. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1002\/JLB.4RU0219-051RR","article-title":"Contribution of IDO to human respiratory syncytial virus infection","volume":"106","author":"Benavente","year":"2019","journal-title":"J. Leukoc. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1093\/infdis\/jir621","article-title":"Opposing biological functions of tryptophan catabolizing enzymes during intracellular infection","volume":"205","author":"Divanovic","year":"2012","journal-title":"J. Infect. Dis."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/12\/8\/865\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:58:02Z","timestamp":1760176682000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/12\/8\/865"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,7]]},"references-count":29,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2020,8]]}},"alternative-id":["v12080865"],"URL":"https:\/\/doi.org\/10.3390\/v12080865","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,7]]}}}