Analysis of infection, integration and tumorigenesis of HTLV-1

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Human T-cell leukemia virus type 1 (HTLV-1) is an etiologic agent of adult T-cell leukemia/lymphoma and other HTLV-1-associated diseases. However, the interaction between HTLV-1 and T cells in the pathogenesis is poorly understood. We successfully infected newborn mouse with HTLV-1-producing human cells, MT-2 cells. For establishing a useful mouse model for HTLV-1 associated diseases, it is important to understand the mechanism of viral-cell interaction in mouse cells. Mouse cells have been reported to be resistant to cell-free HTLV-1 infection. However, recently we reported that HTLV-1 DNA could be observed 24 h after cell-free HTLV-1 infection to mouse cell lines as well as human cell lines. To understand HTLV-1 replication in these cells in detail, we infected mouse T cell lines, EL4 and RLm1, and human T cell line, Molt4, with the concentrated cell-free HTLV-1, produced by c77 feline kidney cell line. Unexpectedly, the amounts of adsorption and entry of HTLV-1 as measured by p19 viral protein at 4 ℃ and 37 ℃, respectively, are 3-fold and 8-fold larger in mouse cells than those in human cells. Moreover, viral DNA was detectable from 1 h in mouse cells but from 3 h in human cells. However, the amount of viral DNA in mouse cells became smaller than that in human cells. The HTLV-1 expression could be detectable until day 2 in mouse cells and until day 4 in human cells. Thus mouse cells would give useful information to dissect the early step of cell-free HTLV-1 infection, especially binding HTLV-1 to cellular receptor.