Distinct Host-Dependent Pathogenic Mechanisms Leading to a Similar Clinical Anemia After Infection with Lymphocytic Choriomeningitis Virus MOHAMMED EL-AZAMI-EL-IDRISSI,* ,2 STE ´ PHANIE FRANQUIN,* ,3 MICHAEL J. DAY ,à GRAZIELLA MAZZA,à CHRISTOPHER J. ELSON,à VE ´ RONIQUE PRE ´ AT , CHARLES J. PFAU,§ AND JEAN-P AUL COUTELIER* ,1 *Unit of Experimental Medicine, Institute for Cellular and Molecular Pathology, and  Unit of Pharmaceutical Technology, Universite ´ Catholique de Louvain, 1200 Bruxelles, Belgium; àDepartment of Pathology & Microbiology, University of Bristol, Bristol BS18 7DU, United Kingdom; and §Department of Biology, Rensselaer Polytechnic Institute, Troy, NY 12181 The Docile strain of lymphocytic choriomeningitis virus (LCMV) induces anemia in a number of inbred strains of mice, including C3HeB/FeJ and CBA/Ht animals. A difference in the kinetics of anemia and in compensatory reticulocytosis suggested that impaired erythropoiesis was the major pathogenic mechanism involved in CBA/Ht mice, but not in C3HeB/FeJ mice. In both mouse strains an antierythrocyte autoantibody production that depended on the presence of functional CD4 þ T lymphocytes was observed. Although depletion of T helper lymphocytes prevented anemia in C3HeB/FeJ mice, this treatment largely failed to inhibit the development of the disease in CBA/Ht animals. This observation indicated that the antierythrocyte autoimmune response induced by the infection was at least partly responsible for the anemia of C3HeB/FeJ mice, but not of CBA/Ht mice. Erythrophagocytosis was enhanced in both mouse strains after LCMV infection, but did not appear to be a major cause of anemia. These data clearly indicate that similar disease profiles induced by the same virus in two different host strains can be the result of distinctly different mechanisms. Exp Biol Med 230:865–871, 2005 Key words: anemia; lymphocytic choriomeningitis virus; antierythrocyte autoantibody; phagocytosis; reticulocytosis Introduction A wide range of pathologies, including choriomeningi- tis, hepatitis, generalized immunosuppression, and endo- crine alterations, may follow infection of mice with lymphocytic choriomeningitis virus (LCMV) (reviewed in Ref. 1). The development of anemia has also been reported after infection with the virus (2–4), but different mecha- nisms may be involved in the pathogenesis of this disease. On the one hand, hematopoietic dysfunction occurs early after infection of different inbred mice and could involve natural killer (NK) cells or production of cytokines, including interferons (4–7). As a consequence, infection with LCMV of the WE strain leads, in immunocompetent mice, to mild aplastic anemia that resolves quickly after infection (4). In perforin-deficient mice chronically infected with the same WE strain of LCMV, a lethal pancytopenia with aplastic anemia develops through tumor necrosis factor and gamma-interferon secretion by CD8 þ T cells (4). In addition, late onset of anemia in immunocompetent C3HeB/ FeJ mice infected with the Docile strain of LCMV correlates with an autoimmune response (2, 3, 8) characterized by the production of antierythrocyte autoantibodies (9, 10). To further analyze the pathogenesis of this anemia, the consequence of infection with the Docile strain of LCMV was compared in C3HeB/FeJ animals and in other mouse strains. Our results indicated that whereas the virus may trigger anemia in several mouse strains, an autoimmune etiology of the disease appears dominant only in C3HeB/FeJ This work was supported by the Fonds National de la Recherche Scientifique (FNRS), Fonds de la Recherche Scientifique Me ´dicale (FRSM), Loterie Nationale, Fonds Spe ´ciaux de Recherche (UCL), North Atlantic Treaty Organization, and the State- Prime Minister’s Office—S.S.T.C. and the French Community (concerted actions), Belgium. The study was also funded by a project grant from the Wellcome Trust and by travel grants from the British Council and C.G.R.I. (Belgian French Community). J.-P.C. is a research director with the FNRS. 1 To whom correspondence should be addressed at Unit of Experimental Medicine, UCL-MEXP 7430, Avenue Hippocrate 74, B-1200 Bruxelles, Belgium. E-mail: coutelier@mexp.ucl.ac.be 2 Current address: Pfizer Maroc, Casablanca, Morocco. 3 Current address: GlaxoSmithKline Biologicals, Rixensart, Belgium. Received April 27, 2005. Accepted August 5, 2005. 865 1535-3702/05/23011-0865$15.00 Copyright Ó 2005 by the Society for Experimental Biology and Medicine