title: Human T-cell lymphotropic virus type-I infection in the severe combined immunodeficiency mouse.
abstract: 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.
authors.affiliation: Neuroimmunology Unit, University of Milano, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Furlan
authors.forename: E F
authors.initials: EF
authors.lastname: Salazar-Grueso
authors.forename: G
authors.initials: G
authors.lastname: Martino
authors.forename: R P
authors.initials: RP
authors.lastname: Roos
authors.forename: E
authors.initials: E
authors.lastname: Brambilla
authors.forename: M
authors.initials: M
authors.lastname: Castellano
authors.forename: J
authors.initials: J
authors.lastname: Cao
authors.forename: F
authors.initials: F
authors.lastname: Lillo
authors.forename: M R
authors.initials: MR
authors.lastname: Terreni
authors.forename: H
authors.initials: H
authors.lastname: Bacellar
authors.forename: F
authors.initials: F
authors.lastname: Dorigatti
authors.forename: L M
authors.initials: LM
authors.lastname: Grimaldi
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western / Q000379:methods; D006800:Deltaretrovirus Infections / Q000276:immunology*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D051379:Mice; D016513:Mice, SCID / Q000276:immunology*; D008875:Middle Aged; D008969:Molecular Sequence Data; D010641:Phenotype; D016133:Polymerase Chain Reaction / Q000379:methods
chemical_list: D007074:Immunoglobulin G