Analysis of infection, integration and tumorigenesis of HTLV-1

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Previously we inoculated HTLV-1 producing cells into newborn mice and demonstrated that Human T-cell Leukemia Virus Type 1 (HTLV-1) could infect mouse. However, the process of viral proliferation and host-virus interaction is poorly understood. Recently we have succeeded in concentrating cell-free virus that retained infectious activity and established an efficient cell-free infection system. Although it was reported that HTLV-1 had low infectivity to mouse cells, we clarified HTLV-1 was able to entry into mouse cells efficiently in this system (Jap.J.Cancer Res.93 : 760-766, 2002).In human carrier, there are little data available on the factors controlling HTLV-1 proviral load. We employed a mouse model of HTLV-1 infection that we had established and found the genetic background as a determinant of HTLV-1 proviral load (Biochem.Biophys.Res.Commun.309 : 161-165, 2003).To clarify the mechanism of carcinogenesis in adult T-cell leukemia, many investigators surveyed the function of Tax protein. On the other hand, in order to investigate the possibility of insertional mutagesesis, we developed the inverse PCR and determined the precise HTLV-1 integration sites on human chromosome. Thirteen of the integration sites (52%) out of isolated 25 integration sites of HTLV-1 from 23 cases of ATL were within genes and the rate were significantly higher than that expected in the case of random integration. Interestingly, some of genes were related to the regulation of cell growth. These results did not conflict of the idea that insertional mutagenesis might contribute to the clonal selection of HTLV-1 infected cells during multistage carcinogenesis of ATL (Cancer Sci.95 : 306-310, 2004).