{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T16:59:54Z","timestamp":1792515594612,"version":"4.5.0"},"reference-count":65,"publisher":"Rockefeller University Press","issue":"3","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1997,2,3]]},"abstract":"<jats:p>The hematologic consequences of infection with the noncytopathic lymphocytic choriomeningitis virus (LCMV) were studied in wild-type mice with inherent variations in their interferon (IFN)-\u03b1\/\u03b2 responder ability and in mutant mice lacking \u03b1\/\u03b2 (IFN-\u03b1\/\u03b2 R0\/0) or \u03b3 IFN (IFN-\u03b3 R0\/0) receptors. During the first week of infection, wild type mice demonstrated a transient pancytopenia. Within a given genetic background, the extent of the blood cell abnormalities did not correlate with the virulence of the LCMV isolate but variations were detected between different mouse strains; they were found to depend on their IFN-\u03b1\/\u03b2 responder phenotype. Whereas IFN-\u03b3 R0\/0 mice were comparable to wild-type mice, IFN-\u03b1\/\u03b2 R0\/0 mice exhibited unchanged peripheral blood values during acute LCMV infection. In parallel, the bone marrow (BM) cellularity, the pluripotential and committed progenitor compartments were up to 30-fold reduced in wild type and IFN-\u03b3 R0\/0, but remained unchanged in IFN-\u03b1\/\u03b2 R0\/0 mice. Viral titers in BM 3 d after LCMV infection were similar in these mice, but antigen localization was different. Viral antigen was predominantly confined to stromal BM in normal mice and IFN-\u03b3 R0\/0 knockouts, whereas, in IFN-\u03b1\/\u03b2 R0\/0 mice, LCMV was detected in &amp;gt;90% of megakaryocytes and 10\u201315% of myeloid precursors, but not in erythroblasts. Although IFN-\u03b1\/\u03b2 efficiently prevented viral replication in potentially susceptible hematopoietic cells, even in overwhelming LCMV infection, unlimited virus multiplication in platelet and myeloid precursors in IFN-\u03b1\/\u03b2 R0\/0 mice did not interfere with the number of circulating blood cells. Natural killer (NK) cell expansion and activity in the BM was comparable on day 3 after infection in mutant and control mice. Adaptive immune responses did not play a major role because comparable kinetics of LCMV-induced pancytopenia and transient depletion of the pluripotential and committed progenitor compartments were observed in CD80\/0 and CD40\/0 mice, in mice depleted of NK cells, in lpr mice, and in perforin-deficient (P0\/0) mice lacking lytic NK cells. Thus, the reversible depression of hematopoiesis during early LCMV infection was not mediated by LCMV-WE\u2013specific cytotoxic T lymphocyte, cytolysis, or secreted IFN-\u03b3 from virally induced NK cells but was a direct effect of IFN-\u03b1\/\u03b2.<\/jats:p>","DOI":"10.1084\/jem.185.3.517","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T12:49:30Z","timestamp":1027687770000},"page":"517-530","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":163,"title":["Virus-induced Transient Bone Marrow Aplasia: Major Role of Interferon-\u03b1\/\u03b2 during Acute Infection with the Noncytopathic Lymphocytic Choriomeningitis Virus"],"prefix":"10.1084","volume":"185","author":[{"given":"Daniel","family":"Binder","sequence":"first","affiliation":[{"name":"From the *Institute of Experimental Immunology, Department of Pathology, University Hospital of Z\u00fcrich, CH-8091 Z\u00fcrich, Switzerland; and the \u2021Division of Hematology, Department of Internal Medicine, University Hospital of Z\u00fcrich, CH-8091 Z\u00fcrich, Switzerland"},{"name":"From the *Institute of Experimental Immunology, Department of Pathology, University Hospital of Z\u00fcrich, CH-8091 Z\u00fcrich, Switzerland; and the \u2021Division of Hematology, Department of Internal Medicine, University Hospital of Z\u00fcrich, CH-8091 Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f6rg","family":"Fehr","sequence":"additional","affiliation":[{"name":"From the *Institute of Experimental Immunology, Department of Pathology, University Hospital of Z\u00fcrich, CH-8091 Z\u00fcrich, Switzerland; and the \u2021Division of Hematology, Department of Internal Medicine, University Hospital of Z\u00fcrich, CH-8091 Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Hengartner","sequence":"additional","affiliation":[{"name":"From the *Institute of Experimental Immunology, Department of Pathology, University Hospital of Z\u00fcrich, CH-8091 Z\u00fcrich, Switzerland; and the \u2021Division of Hematology, Department of Internal Medicine, University Hospital of Z\u00fcrich, CH-8091 Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolf M.","family":"Zinkernagel","sequence":"additional","affiliation":[{"name":"From the *Institute of Experimental Immunology, Department of Pathology, University Hospital of Z\u00fcrich, CH-8091 Z\u00fcrich, Switzerland; and the \u2021Division of Hematology, Department of Internal Medicine, University Hospital of Z\u00fcrich, CH-8091 Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[1997,2,3]]},"reference":[{"key":"2023072507135976500_B1","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/0268-960X(91)90037-D","article-title":"Viruses and bone marrow failure","volume":"5","author":"Rosenfeld","year":"1991","journal-title":"Blood Rev"},{"key":"2023072507135976500_B2"},{"key":"2023072507135976500_B3","first-page":"38","article-title":"The effect of cytomegalovirus on hemopoiesis: in vitro evidence for selective infection of marrow stromal cells","volume":"17","author":"Apperley","year":"1989","journal-title":"Exp Hematol"},{"key":"2023072507135976500_B4","doi-asserted-by":"crossref","first-page":"2476","DOI":"10.1182\/blood.V76.12.2476.2476","article-title":"Lack of evidence for infection of or effect on growth of hematopoietic progenitor cells after in vivo or in vitro exposure to human immunodeficiency virus","volume":"76","author":"Molina","year":"1990","journal-title":"Blood"},{"key":"2023072507135976500_B5","first-page":"264","article-title":"Aplastic anemia following infectious mononucleosis: possible immune etiology","volume":"7","author":"Shadduck","year":"1979","journal-title":"Exp Hematol"},{"key":"2023072507135976500_B6","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1111\/j.1365-2141.1990.tb06339.x","article-title":"Post-hepatitis aplastic anemia in children in Taiwan, a hepatitis prevalent area","volume":"74","author":"Liang","year":"1990","journal-title":"Br J Haematol"},{"key":"2023072507135976500_B7","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/S0065-2776(08)60197-2","article-title":"The virology and immunobiology of lymphocytic choriomeningitis virus infection","volume":"30","author":"Buchmeier","year":"1980","journal-title":"Adv Immunol"},{"key":"2023072507135976500_B8","first-page":"1","article-title":"The arenaviruses\u2014an introduction","volume":"133","author":"Oldstone","year":"1987","journal-title":"Curr Topics Microbiol Immun"},{"key":"2023072507135976500_B9","first-page":"1","article-title":"Lymphocytic choriomeningitis virus","volume":"10","author":"Lehmann-Grube","year":"1971","journal-title":"Monogr Virol"},{"key":"2023072507135976500_B10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000391864","article-title":"Persistent and slow virus infections","volume":"3","author":"Hotchin","year":"1971","journal-title":"Monogr Virol"},{"key":"2023072507135976500_B11","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1093\/oxfordjournals.aje.a112076","article-title":"Outbreak of lymphocytic choriomeningitis virus infections in medical center personnel","volume":"101","author":"Hinmann","year":"1975","journal-title":"Am J Epidemiol"},{"key":"2023072507135976500_B12"},{"key":"2023072507135976500_B13"},{"key":"2023072507135976500_B14","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/S0065-3527(08)60777-0","article-title":"The interplay between lymphocytic choriomeningitis virus, immune function, and hemopoiesis in mice","volume":"22","author":"Bro-J\u00f8rgensen","year":"1978","journal-title":"Adv Virus Res"},{"key":"2023072507135976500_B15","first-page":"259","article-title":"Severe and transient pancytopenia associated with a chronic arenavirus infection","volume":"3","author":"Broomhall","year":"1987","journal-title":"J Exp Pathol"},{"key":"2023072507135976500_B16","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1128\/iai.19.2.533-539.1978","article-title":"Mechanisms of hemopoietic and immunological dysfunction induced by lymphocytic choriomeningitis virus","volume":"19","author":"Silberman","year":"1978","journal-title":"Infect Immun"},{"key":"2023072507135976500_B17","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1128\/jvi.59.2.428-433.1986","article-title":"Mechanisms of lymphocytic choriomeningitis virusinduced hemopoietic dysfunction","volume":"59","author":"Thomsen","year":"1986","journal-title":"J Virol"},{"key":"2023072507135976500_B18","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.4049\/jimmunol.117.5_Part_1.1495","article-title":"H-2 compatibility requirement for virus-specific T cell\u2013mediated effector functions in vivo. 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