High simian T-cell leukemia virus type 1 proviral loads combined with genetic stability as a result of cell-associated provirus replication in naturally infected, asymptomatic monkeys
✍ Scribed by Anne-Sophie Gabet; Antoine Gessain; Eric Wattel
- Publisher
- John Wiley and Sons
- Year
- 2003
- Tongue
- French
- Weight
- 216 KB
- Volume
- 107
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
Abstract
Simian T‐cell leukemia virus type 1 (STLV‐1) is a primate T cell leukemia virus of the group of oncogenic delta retroviruses. Sharing a high level of genetic homology with human T cell leukemia virus type 1 (HTLV‐1), it is etiologically linked to the development of simian T cell malignancies that closely resemble HTLV‐1 associated leukemias and lymphomas and might thus constitute an interesting model of study. The precise nature of STLV‐1 replication in vivo remains unknown. The STLV‐1 circulating proviral load of 14 naturally infected Celebes macaques (Macaca tonkeana) was measured by real‐time quantitative PCR. The mean proportion of infected peripheral mononuclear cells was 7.9%, ranging from <0.4% to 38.9%. Values and distributions were closely reminiscent of those observed in symptomatic and asymptomatic HTLV‐1 infected humans. Sequencing more than 32 kb of LTRs deriving from 2 animals with high proviral load showed an extremely low STLV‐1 genetic variability (0.113%). This paradoxical combination of elevated proviral load and remarkable genetic stability was finally explained by the demonstration of a cell‐associated dissemination of the virus in vivo. Inverse PCR (IPCR) amplification of STLV‐1 integration sites evidenced clones of infected cells in all infected animals. The pattern of STLV‐1 replication in these asymptomatic monkeys was indistinguishable from that of HTLV‐1 in asymptomatic carriers or in patients with inflammatory diseases. We conclude that, as HTLV‐1, STLV‐1 mainly replicates by the clonal expansion of infected cells; accordingly, STLV‐1 natural monkey infection constitutes an appropriate and promising model for the study of HTLV‐1 associated leukemogenesis in vivo. © 2003 Wiley‐Liss, Inc.