Human T-cell lymphotropic virus type-I infection in the severe combined immunodeficiency mouse.
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.
Furlan
R
R
Neuroimmunology Unit, University of Milano, Italy.
Salazar-Grueso
E F
EF
Martino
G
G
Roos
R P
RP
Brambilla
E
E
Castellano
M
M
Cao
J
J
Lillo
F
F
Terreni
M R
MR
Bacellar
H
H
Dorigatti
F
F
Grimaldi
L M
LM
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
D007074:Immunoglobulin G