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Journal of Virology, May 2000, p. 4860-4867, Vol. 74, No. 10
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Lymphoid Organs as a Major Reservoir for Human T-Cell Leukemia Virus Type 1 in Experimentally Infected Squirrel Monkeys (Saimiri sciureus): Provirus Expression, Persistence, and Humoral and Cellular Immune Responses

Mirdad Kazanji,1,2,* Abel Ureta-Vidal,3 Simona Ozden,4 Frédéric Tangy,4 Benoit de Thoisy,5 Laurence Fiette,6 Antoine Talarmin,2 Antoine Gessain,1 and Guy de Thé1

Unité d'Oncologie Virale1 and Unité des Virus Lents,4 CNRS-URA D1930, Unité d'Immunité Cellulaire Antivirale,3 and Unité d'Histopathologie,6 Institut Pasteur, Paris, France, and Laboratoire de Rétrovirologie2 and Centre de Primatologie,5 Institut Pasteur de la Guyane, Cayenne, French Guiana

Received 10 August 1999/Accepted 17 February 2000

The aim of this study was to investigate the distribution of human T-cell leukemia virus type 1 (HTLV-1) in various organs of serially sacrificed squirrel monkeys (Saimiri sciureus) in order to localize the reservoir of the virus and to evaluate the relationship between viral expression and the humoral or cellular immune response during infection. Six squirrel monkeys infected with HTLV-1 were sacrificed 6, 12, and 35 days and 3, 6, and 26 months after inoculation, and 20 organs and tissues were collected from each animal. PCR and reverse transcription-PCR (RT-PCR) were performed with gag and tax primers. Proviral DNA was detected by PCR in peripheral blood mononuclear cells (PBMCs) of monkeys sacrificed 6 days after inoculation and in PBMCs, spleens, and lymph nodes of monkeys sacrificed 12 and 35 days and 3, 6, and 26 months after inoculation. Furthermore, tax/rex mRNA was detected by RT-PCR in the PBMCs of two monkeys 8 to 12 days after inoculation and in the spleens and lymph nodes of the monkey sacrificed on day 12. In this animal, scattered HTLV-1 tax/rex mRNA-positive lymphocytes were detected by in situ hybridization in frozen sections of the spleen, around the germinal centers and close to the arterial capillaries. Anti-HTLV-1 cell-mediated immunity was evaluated at various times after inoculation. Anti-p40Tax and anti-Env cytolytic T-cell responses were detected 2 months after infection and remained detectable thereafter. When Tax peptides were used, this response appeared to be directed against various Tax epitopes. Our results indicate that squirrel monkeys represent a promising animal model for studying the early events of HTLV-1 infection and for evaluating candidate vaccines against HTLV-1.

* Corresponding author. Mailing address: Laboratoire de Rétrovirologie, Institut Pasteur de la Guyane, B.P. 6010, 23, Av. Pasteur, 97300 Cayenne, French Guiana. Phone: 594 29 68 44. Fax: 594 30 94 16. E-mail: mkazanji{at}pasteur-cayenne.fr.

Journal of Virology, May 2000, p. 4860-4867, Vol. 74, No. 10
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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