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Human T‐cell lymphotropic virus type‐I infection in the severe combined immunodeficiency mouse
Author(s) -
Furlan Roberto,
SalazarGrueso Edgar F.,
Martino Gianvito,
Roos Raymond P.,
Brambilla Elena,
Castellano Marina,
Cao Jajun,
Lillo Flavia,
Terreni Maria Rosa,
Bacellar Haroldo,
Dorigatti Fernanda,
Grimaldi Luigi M.E.
Publication year - 1996
Publication title -
journal of medical virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.782
H-Index - 121
eISSN - 1096-9071
pISSN - 0146-6615
DOI - 10.1002/(sici)1096-9071(199606)49:2<77::aid-jmv1>3.0.co;2-g
Subject(s) - tropical spastic paraparesis , virology , tropism , virus , lymphoma , biology , human t lymphotropic virus , immunology , human t lymphotropic virus 1 , myelopathy , severe combined immunodeficiency , t cell , antibody , pathogenesis , medicine , t cell leukemia , gene , spinal cord , immune system , biochemistry , neuroscience
Human T‐cell lymphotropic virus type‐I (HTLV‐I) is the etiologic agent of HTLV‐I‐associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T‐cell leukemia (ATL). HAM/TSP and ATL occur infrequently among HTLV‐I‐infected individuals, and rarely develop in the same individual. To study host and viral factors involved in the induction, tissue tropism, as well as pathogenesis of HAM/TSP, peripheral blood lymphocytes (PBL) from 14 patients with HAM/TSP and from 9 controls were introduced into severe combined immunodeficiency (SCID) mice by intraperitoneal injection. Mice were followed for up to 26 weeks. Human IgG was produced from 2 to 14 weeks after reconstitution in all animals. Thirty‐two of 44 mice (72%) showed circulating human antibody against the major viral protein products of HTLV‐I. Analysis of viral sequences by polymerase chain reaction (PCR) demonstrated HTLV‐I sequences in 21/38 (55%) brains and in 7/17 (41%) spinal cords from HTLV‐I‐hu SCID mice. No animal had clinical evidence of neurological impairment or pathological findings similar to those seen in HAM/TSP. Seven mice who received PBL from Epstein Barr virus (EBV)‐seropositive patients developed an intraperitoneal lymphoma. In 2 mice an infiltration of brain by a lymphoblastic tumor of B/T cell type was observed. By PCR, all the tumors were EBV‐positive; HTLV‐I sequences were detected in 5 of them. Our study suggests that the HTLV‐I‐hu‐SCID mouse provides a potentially valuable system for studying the production, kinetics, and pathogenicity of anti‐HTLV‐I antibody, and may help clarify the interaction of EBV and retroviruses in the development of disease. © 1996 Wiley‐Liss, Inc.