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 indi vidual. To study host and viral factors involved in the induction, tis sue tropism, as well as pathogenesis of HAM/TSP, peripheral blood lymp hocytes (PBL) from 14 patients with HAM/TSP and from 9 controls were i ntroduced into severe combined immunodeficiency (SCID) mice by intrape ritoneal injection. Mice were followed for up to 26 weeks. Human IgG w as produced from 2 to 14 weeks after reconstitution in all animals. Th irty-two of 44 mice (72%) showed circulating human antibody against th e 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 mi ce. No animal had clinical evidence of neurological impairment or path ological findings similar to those seen in HAM/TSP. Seven mice who rec eived PBL from Epstein Barr virus (EBV)-seropositive patients develope d 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 tu mors were EBV-positive; HTLV-I sequences were detected in 5 of them. O ur study suggests that the HTLV-I-hu-SCID mouse provides a potentially valuable system for studying the production, kinetics, and pathogenic ity of anti-HTLV-I antibody, and may help clarify the interaction of E BV and retroviruses in the development of disease. (C) 1996 Wiley-Liss , Inc.