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Journal of Virology, January 2001, p. 1083-1089, Vol. 75, No. 2
Unité 524 INSERM, Institut de Recherche
sur le Cancer de Lille, Lille,1
Unité d'Oncogenèse Virale, UMR5537
CNRS-Université Claude Bernard, Centre Léon Bérard,
Lyon,2 France, and Laboratoire de
Rétrovirologie3 and Centre de
Primatologie,4 Institut Pasteur de la Guyane,
Cayenne, Guyane Française
Received 11 August 2000/Accepted 25 October 2000
After experimental infection of squirrel monkeys (Saimiri
sciureus) with human T-cell leukemia virus type 1 (HTLV-1)-infected cells, the virus is transcribed only transiently in
circulating blood, spleen, and lymph nodes. Stable disappearance of
viral expression occurs at 2 to 3 weeks after inoculation. This
coincides with the development of the anti-HTLV-1 immune response and
persistent detection of the provirus in peripheral blood mononuclear
cells (PBMCs). In this study, the HTLV-1 replication pattern was
analyzed over time in PBMCs and various organs from two HTLV-1-infected squirrel monkeys. Real-time quantitative PCR confirmed that PBMCs and
lymphoid organs constitute the major reservoirs for HTLV-1. The PCR
amplification of HTLV-1 flanking sequences from PBMCs evidenced a
pattern of clonal expansion of infected cells identical to that
observed in humans. Dissemination of the virus in body compartments
appeared to result from cellular transport of the integrated provirus.
The circulating proviral burden increased as a function of time in one
animal studied over a period of 4 years. The high proviral loads
observed in the last samples resulted from the accumulation of infected
cells via the extensive proliferation of a restricted number of
persistent clones on a background of polyclonally expanded
HTLV-1-positive cells. Therefore, HTLV-1 primary infection in squirrel
monkeys is a two-step process involving a transient phase of reverse
transcription followed by persistent multiplication of infected cells.
This suggests that the choice of the target for blocking HTLV-1
replication might depend on the stage of infection.
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.2.1083-1089.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Two-Step Nature of Human T-Cell Leukemia Virus Type 1 Replication
in Experimentally Infected Squirrel Monkeys (Saimiri
sciureus)
*
Corresponding author. Mailing address: Unité
d'Oncogenèse Virale, UMR5537-CNRS, Université Claude
Bernard, Centre Léon-Bérard, 28, rue Laënnec, 69373 Lyon cedex 08, France. Phone: 334 78 78 26 69. Fax: 334 78 78 27 17. E-mail: wattel{at}lyon.fnclcc.fr.
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