Human T-cell lymphotropic virus type-I infection in the severe combined immunodeficiency mouse

Roberto Furlan, Edgar F. Salazar-Grueso, Gianvito Martino, Raymond P. Roos, Elena Brambilla, Marina Castellano, Jajun Cao, Flavia Lillo, Maria Rosa Terreni, Haroldo Bacellar, Fernanda Dorigatti, Luigi M E Grimaldi

Research output: Contribution to journalArticlepeer-review

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-l antibody, and may help clarify the interaction of EBV and retroviruses in the development of disease.

Original languageEnglish
Pages (from-to)77-82
Number of pages6
JournalJournal of Medical Virology
Volume49
Issue number2
DOIs
Publication statusPublished - Jun 1996

Keywords

  • ATL
  • EBV
  • HAM/TSP
  • HTLV-I
  • SCID mouse
  • Tumorigenesis

ASJC Scopus subject areas

  • Virology

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