{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:43:39Z","timestamp":1760197419503,"version":"build-2065373602"},"reference-count":37,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2018,5,2]],"date-time":"2018-05-02T00:00:00Z","timestamp":1525219200000},"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>(1) Background: Small ruminant lentiviruses (SRLV) persist in infected goats that mount a strong humoral immune response characterized by low neutralizing titers. In this study, we characterized the antibody response to SU5, a variable, immunodominant epitope of the envelope glycoprotein of SRLV. We tested the working hypothesis that the variability of SU5 reflects escape from neutralizing antibody. (2) Methods: Affinity purified anti-SU5 antibody were tested for their neutralizing activity to the homologous lentivirus. Virus culture supernatant\u2014in native form or following sonication and filtration\u2014was used to test the ability of free envelope glycoproteins to compete for binding in a SU5-peptide-ELISA. (3) Results: Anti-SU5 antibodies are not neutralizing, strongly suggesting that they do not bind intact viral particles. In contrast, shed envelope glycoproteins efficiently compete for binding in a SU5-ELISA, providing convincing evidence that the SU5 epitope is exposed only on shed envelope glycoproteins. (4) Conclusions: Our results show that the antibody engaging SU5 is not neutralizing and does not appear to bind to SU expressed at the surface of virus particles. We propose that SU5 is a potential decoy epitope exposed on shaded envelope glycoproteins, luring the humoral immune response in committing an original antigenic sin to a functionally irrelevant epitope.<\/jats:p>","DOI":"10.3390\/v10050231","type":"journal-article","created":{"date-parts":[[2018,5,3]],"date-time":"2018-05-03T03:20:27Z","timestamp":1525317627000},"page":"231","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["An Immunodominant Region of the Envelope Glycoprotein of Small Ruminant Lentiviruses May Function as Decoy Antigen"],"prefix":"10.3390","volume":"10","author":[{"given":"Marie-Luise","family":"Zahno","sequence":"first","affiliation":[{"name":"Institute of Virology and Immunology, Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern and Federal Department of Home Affairs, CH-3012 Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1469-4723","authenticated-orcid":false,"given":"Giuseppe","family":"Bertoni","sequence":"additional","affiliation":[{"name":"Institute of Virology and Immunology, Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern and Federal Department of Home Affairs, CH-3012 Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2018,5,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"94","DOI":"10.2174\/157016210790416415","article-title":"Srlvs: A genetic continuum of lentiviral species in sheep and goats with cumulative evidence of cross species transmission","volume":"8","author":"Leroux","year":"2010","journal-title":"Curr. HIV Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1867","DOI":"10.3390\/v5071867","article-title":"Small ruminant lentiviruses (SRLVs) break the species barrier to acquire new host range","volume":"5","author":"Singh","year":"2013","journal-title":"Viruses"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.cimid.2011.12.003","article-title":"Small ruminant lentiviruses: Immunopathogenesis of visna-maedi and caprine arthritis and encephalitis virus","volume":"35","author":"Blacklaws","year":"2012","journal-title":"Comp. Immunol. Microbiol. Infect. Dis."},{"key":"ref_4","unstructured":"Tempesta, M. (2016). Small ruminant lentivirus infections in goats. Recent Adavances in Goat Diseases, International Veterinary Information Service."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2396","DOI":"10.1128\/jvi.64.5.2396-2398.1990","article-title":"Severity of arthritis is predicted by antibody response to gp135 in chronic infection with caprine arthritis- encephalitis virus","volume":"64","author":"Knowles","year":"1990","journal-title":"J. Virol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1974","DOI":"10.1128\/jvi.62.6.1974-1980.1988","article-title":"Sialic acid on the surface of caprine arthritis-encephalitis virus define the biological properties of the virus","volume":"62","author":"Huso","year":"1988","journal-title":"J. Virol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"6178","DOI":"10.1128\/JVI.74.13.6178-6185.2000","article-title":"Variability and immunogenicity of caprine arthritis-encephalitis virus surface glycoprotein","volume":"74","author":"Valas","year":"2000","journal-title":"J. Virol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2929","DOI":"10.1099\/0022-1317-81-12-2929","article-title":"B-cell epitopes of the envelope glycoprotein of caprine arthritis-encephalitis virus and antibody response in infected goats","volume":"81","author":"Bertoni","year":"2000","journal-title":"J. Gen. Virol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1128\/JCM.44.3.981-991.2006","article-title":"Analysis of the antibody response to an immunodominant epitope of the envelope glycoprotein of a lentivirus and its diagnostic potential","volume":"44","author":"Mordasini","year":"2006","journal-title":"J. Clin. Microbiol."},{"key":"ref_10","unstructured":"Rackwitz, R., Pees, M., Aschenbach, J.R., and G\u00e4bel, G. (2014). SU5 serology as a novel tool to support a challenging caprine arthritis encephalitis virus (CAEV) eradication campaign. Lbh: 7. Leipziger Tier\u00e4rztekongress, University of Leipzig."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1099\/vir.0.83410-0","article-title":"Mutational analysis of a principal neutralization domain of visna\/maedi virus envelope glycoprotein","volume":"89","author":"Haflidadottir","year":"2008","journal-title":"J. Gen. Virol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2543","DOI":"10.1099\/0022-1317-83-10-2543","article-title":"Selection of antigenic variants in maedi-visna virus infection","volume":"83","author":"Andresdottir","year":"2002","journal-title":"J. Gen. Virol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1128\/jvi.58.2.665-670.1986","article-title":"Sequence homology between cloned caprine arthritis encephalitis virus and visna virus, two neurotropic lentiviruses","volume":"58","author":"Pyper","year":"1986","journal-title":"J. Virol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.virol.2006.02.014","article-title":"Viral load, organ distribution, histopathological lesions, and cytokine mRNA expression in goats infected with a molecular clone of the caprine arthritis encephalitis virus","volume":"350","author":"Ravazzolo","year":"2006","journal-title":"Virology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/0042-6822(90)90303-9","article-title":"Nucleotide sequence and transcriptional analysis of molecular clones of CAEV which generate infectious virus","volume":"179","author":"Saltarelli","year":"1990","journal-title":"Virology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"7139","DOI":"10.1128\/jvi.68.11.7139-7147.1994","article-title":"Antibody reactivity to the immunodominant epitopes of the caprine arthritis-encephalitis virus gp38 transmembrane protein associates with the development of arthritis","volume":"68","author":"Bertoni","year":"1994","journal-title":"J. Virol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1093\/infdis\/171.2.328","article-title":"Depressed CD4+ T lymphocyte proliferative response and enhanced antibody response to viral antigen in chronic lentivirus- induced arthritis","volume":"171","author":"Perry","year":"1995","journal-title":"J. Infect. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3488","DOI":"10.1128\/jvi.62.9.3488-3492.1988","article-title":"Antigenic variation of neutralization-sensitive epitopes of caprine arthritis-encephalitis lentivirus during persistent arthritis","volume":"62","author":"McGuire","year":"1988","journal-title":"J. Virol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1647","DOI":"10.1093\/bioinformatics\/bts199","article-title":"Geneious basic: An integrated and extendable desktop software platform for the organization and analysis of sequence data","volume":"28","author":"Kearse","year":"2012","journal-title":"Bioinformatics"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1016\/j.vetmic.2012.11.017","article-title":"Virological and phylogenetic characterization of attenuated small ruminant lentivirus isolates eluding efficient serological detection","volume":"162","author":"Cardinaux","year":"2013","journal-title":"Vet. Microbiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"8064","DOI":"10.1128\/JVI.73.10.8064-8072.1999","article-title":"Naturally occurring mutations within 39 amino acids in the envelope glycoprotein of maedi-visna virus alter the neutralization phenotype","volume":"73","author":"Skraban","year":"1999","journal-title":"J. Virol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1016\/j.cell.2014.01.052","article-title":"Structural insights on the role of antibodies in HIV-1 vaccine and therapy","volume":"156","author":"West","year":"2014","journal-title":"Cell"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1146\/annurev.immunol.24.021605.090557","article-title":"Gp120: Target for neutralizing HIV-1 antibodies","volume":"24","author":"Pantophlet","year":"2006","journal-title":"Annu. Rev. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"279","DOI":"10.4049\/jimmunol.159.1.279","article-title":"Refocusing neutralizing antibody response by targeted dampening of an immunodominant epitope","volume":"159","author":"Garrity","year":"1997","journal-title":"J. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/S0065-2776(01)77018-6","article-title":"The antiviral activity of antibodies in vitro and in vivo","volume":"77","author":"Parren","year":"2001","journal-title":"Adv. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1006\/viro.1996.0394","article-title":"Restrictive type of replication of ovine\/caprine lentiviruses in ovine fibroblast cell cultures","volume":"222","author":"Chebloune","year":"1996","journal-title":"Virology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"5744","DOI":"10.1128\/jvi.65.11.5744-5750.1991","article-title":"Structure and genetic variability of envelope glycoproteins of two antigenic variants of caprine arthritis-encephalitis lentivirus","volume":"65","author":"Knowles","year":"1991","journal-title":"J. Virol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.virol.2005.05.028","article-title":"Mutations increasing exposure of a receptor binding site epitope in the soluble and oligomeric forms of the caprine arthritis-encephalitis lentivirus envelope glycoprotein","volume":"339","author":"Hotzel","year":"2005","journal-title":"Virology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"11578","DOI":"10.1128\/JVI.77.21.11578-11587.2003","article-title":"Caprine arthritis-encephalitis virus envelope surface glycoprotein regions interacting with the transmembrane glycoprotein: Structural and functional parallels with human immunodeficiency virus type 1 gp120","volume":"77","author":"Hotzel","year":"2003","journal-title":"J. Virol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"9190","DOI":"10.1128\/JVI.78.17.9190-9202.2004","article-title":"Glycosylation of immunodominant linear epitopes in the carboxy-terminal region of the caprine arthritis-encephalitis virus surface envelope enhances vaccine-induced type-specific and cross-reactive neutralizing antibody responses","volume":"78","author":"Trujillo","year":"2004","journal-title":"J. Virol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1084\/jem.104.1.85","article-title":"A serologic recapitulation of past experiences with influenza A; antibody response to monovalent vaccine","volume":"104","author":"Davenport","year":"1956","journal-title":"J. Exp. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1038\/nm0497-366d","article-title":"HIV-1 antibody\u2014Debris or virion?","volume":"3","author":"Parren","year":"1997","journal-title":"Nat. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1016\/j.bbrc.2018.01.141","article-title":"The level of decoy epitope in PCV2 vaccine affects the neutralizing activity of sera in the immunized animals","volume":"496","author":"Jin","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"6358","DOI":"10.1016\/j.vaccine.2016.10.044","article-title":"Replacing the decoy epitope of PCV2b capsid protein with a protective epitope enhances efficacy of PCV2b vaccine","volume":"34","author":"Yu","year":"2016","journal-title":"Vaccine"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2221","DOI":"10.1099\/0022-1317-70-8-2221","article-title":"Modulation of lentivirus replication by antibodies. Non-neutralizing antibodies to caprine arthritis-encephalitis virus enhance early stages of infection in macrophages, but do not cause increased production of virions","volume":"70","author":"Jolly","year":"1989","journal-title":"J. Gen. Virol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1016\/0006-291X(90)90402-9","article-title":"Relative positioning of the T cell and B cell determinants on an immunogenic peptide: Its influence on antibody response","volume":"169","author":"Hachimura","year":"1990","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1589","DOI":"10.1099\/vir.0.82800-0","article-title":"Vaccination with a T-cell-priming Gag peptide of caprine arthritis encephalitis virus enhances virus replication transiently in vivo","volume":"88","author":"Nenci","year":"2007","journal-title":"J. Gen. Virol."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/10\/5\/231\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:02:53Z","timestamp":1760194973000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/10\/5\/231"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,5,2]]},"references-count":37,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2018,5]]}},"alternative-id":["v10050231"],"URL":"https:\/\/doi.org\/10.3390\/v10050231","relation":{},"ISSN":["1999-4915"],"issn-type":[{"type":"electronic","value":"1999-4915"}],"subject":[],"published":{"date-parts":[[2018,5,2]]}}}