{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T01:34:16Z","timestamp":1788572056752,"version":"build-2803163510"},"reference-count":41,"publisher":"American Society for Microbiology","issue":"21","license":[{"start":{"date-parts":[[2007,11,1]],"date-time":"2007-11-01T00:00:00Z","timestamp":1193875200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2007,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Lymphocytic choriomeningitis virus (LCMV) is a murine arenavirus whose glycoprotein consists of a transmembrane subunit (GP-2) and a receptor-binding subunit (GP-1). LCMV-neutralizing antibodies (nAbs) are directed against a single site on GP-1 and occur 1 month after the infection of cytotoxic-T-lymphocyte (CTL) deficient mice. In wild-type mice, however, CTLs control early infection, and weak nAb titers emerge very late (after 70 to 150 days) if at all. Production of recombinant GP-1 in native conformation enabled us to study the emergence of GP-1-binding antibodies directed against the neutralizing epitope. By combining binding and neutralization assays, we correlated the development of binding antibodies versus nAbs in wild-type and CTL-deficient mice after infection with different LCMV doses. We found that wild-type mice developed GP-1-specific antibodies already by day 8 after exposure to high but not low doses, demonstrating that naive GP-1-specific B cells were infrequent. Furthermore, the induced antibodies bound to the neutralizing GP-1 epitope but failed to neutralize the virus and therefore were of low affinity. In CTL-deficient mice, where massive viremia quickly levels initial differences in viral load, low and high doses induced low-affinity non-neutralizing GP-1-binding antibodies with kinetics similar to high-dose-infected wild-type mice. Only in CTL-deficient mice, however, the GP-1-specific antibodies developed into nAbs within 1 month. We conclude that LCMV uses a dual strategy to evade nAb responses in wild-type mice. First, LCMV exploits a \u201chole\u201d in the murine B-cell repertoire, which provides only a small and narrow initial pool of low-affinity GP-1-specific B cells. Second, affinity maturation of the available low-affinity non-neutralizing antibodies is impaired.<\/jats:p>","DOI":"10.1128\/jvi.00955-07","type":"journal-article","created":{"date-parts":[[2007,8,16]],"date-time":"2007-08-16T00:18:25Z","timestamp":1187223505000},"page":"11650-11657","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":49,"title":["Early Antibodies Specific for the Neutralizing Epitope on the Receptor Binding Subunit of the Lymphocytic Choriomeningitis Virus Glycoprotein Fail To Neutralize the Virus"],"prefix":"10.1128","volume":"81","author":[{"given":"Bruno","family":"Eschli","sequence":"first","affiliation":[{"name":"Institute of Experimental Immunolgy, University Hospital Zu\u0308rich, Schmelzbergstrasse 12, CH-8091 Zu\u0308rich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raphae\u0308l M.","family":"Zellweger","sequence":"additional","affiliation":[{"name":"Institute of Experimental Immunolgy, University Hospital Zu\u0308rich, Schmelzbergstrasse 12, CH-8091 Zu\u0308rich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Wepf","sequence":"additional","affiliation":[{"name":"Institute of Experimental Immunolgy, University Hospital Zu\u0308rich, Schmelzbergstrasse 12, CH-8091 Zu\u0308rich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl S.","family":"Lang","sequence":"additional","affiliation":[{"name":"Institute of Experimental Immunolgy, University Hospital Zu\u0308rich, Schmelzbergstrasse 12, CH-8091 Zu\u0308rich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"Quirin","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, ETH Zu\u0308rich, Schafmattstrasse 18, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline","family":"Weber","sequence":"additional","affiliation":[{"name":"Institute of Experimental Immunolgy, University Hospital Zu\u0308rich, Schmelzbergstrasse 12, CH-8091 Zu\u0308rich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolf M.","family":"Zinkernagel","sequence":"additional","affiliation":[{"name":"Institute of Experimental Immunolgy, University Hospital Zu\u0308rich, Schmelzbergstrasse 12, CH-8091 Zu\u0308rich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Hengartner","sequence":"additional","affiliation":[{"name":"Institute of Experimental Immunolgy, University Hospital Zu\u0308rich, Schmelzbergstrasse 12, CH-8091 Zu\u0308rich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830220720"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0166-0934(91)90018-U"},{"key":"e_1_3_2_4_2","doi-asserted-by":"crossref","first-page":"5408","DOI":"10.4049\/jimmunol.151.10.5408","volume":"151","year":"1993","unstructured":"Battegay, M., D. 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