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.
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.
Gabet
Anne-Sophie
AS
Unité d'Oncogenèse Virale, Centre Léon Bérard, Lyon, France.
Gessain
Antoine
A
Wattel
Eric
E
D000818:Animals; D002460:Cell Line; D003001:Cloning, Molecular; D017931:DNA Primers; D004279:DNA, Viral / Q000032:analysis; D006800:Deltaretrovirus Infections / Q000235:genetics / Q000473:pathology / Q000662:veterinary*; D005260:Female; D005814:Genes, Viral / Q000502:physiology*; D016355:Genes, pX / Q000235:genetics; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology; D008251:Macaca / Q000821:virology; D008297:Male; D008992:Monkey Diseases / Q000235:genetics / Q000473:pathology / Q000821:virology*; D016133:Polymerase Chain Reaction; D011533:Proviruses / Q000502:physiology*; D015303:Simian T-lymphotropic virus 1 / Q000502:physiology*; D019562:Viral Load; D014779:Virus Replication / Q000502:physiology*
D017931:DNA Primers; D004279:DNA, Viral