Human T-cell leukemia virus type 1 (HTLV-1) infection of mice: Proliferation of cell clones with integrated HTLV-1 provirus in lymphoid organs

Human T-cell leukemia virus type 1 (HTLV-1) is suggested to cause adult T-c ell leukemia after 40 to 50 years of latency in a small percentage of carri ers, However, little is known about the pathophysiology of the latent perio d and the reservoir organs where polyclonal proliferation of cells harborin g integrated provirus occurs, The availability of animal models would be us eful to analyze the latent period of HTLV-1 infection. At 18 months after H TLV-1 infection of C3H/HeJ mice inoculated with the MT-2 cell line, which i s an HTLF-1-producing human T-cell line, HTLV-1 provirus was detected in sp leen DNA from eight of nine mice. No more than around 100 proviruses were f ound per 10(5) spleen cells. Cellular sequences flanking the 3 ' long termi nal repeat (LTR) and the clonalities of the cells which harbor integrated H TLV-1 provirus were analyzed hy linker-mediated PCR, The results showed tha t the flanking sequences are of mouse genome origin and that polyclonal pro liferation of the spleen cells harboring integrated HTLV-1 provirus had occ urred in three mice. A sequence flanking the 5 ' LTR was isolated from one of the mice and revealed the presence of a 6-nucleotide duplication of cell ular sequences, consistent with typical retroviral integration. Moreover, P CR was performed on DNA from infected tissues, with LTR primers and primers derived from seven novel flanking sequences of the three mice. Data reveal ed that the expected PCR products were found from lymphatic tissues of the same mouse, suggesting that the lymphatic tissues were the reservoir organs for the infected and proliferating cell clones. The mouse model described here should be useful for analysis of the carrier state of HTLV-1 infection in humans.