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J. Virol. doi:10.1128/JVI.01009-06
Copyright (c) 2006, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

De novo HTLV-I Infection of Human Lymphocytes in Nonobese Diabetic-SCID, Common -Chain Knocked-Out Mice

Laboratory of Virus Immunology, Laboratory of Virus Pathogenesis, Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan, Department of Hematology and Department of Infectious Diseases, Graduate School of Medicine, Kumamoto University, Kumamoto 860-8556, Japan

^* To whom correspondence should be addressed. Email: mmatsuok{at}virus.kyoto-u.ac.jp.

	Abstract

Human T-cell leukemia virus type I (HTLV-I) is the etiologic agent of adult T-cell leukemia (ATL), a disease that is triggered after a long latency period. HTLV-I is known to spread through cell-to-cell contact. In an attempt to study the events in early stages of HTLV-I infection, we inoculated uninfected human peripheral blood mononuclear cells and the HTLV-I-producing cell line MT-2, into NOD-SCID common -chain knocked-out (NOG) mice. HTLV-I infection was confirmed with the detection of proviral DNA in recovered samples. Both CD4⁺ and CD8⁺ T cells were found to harbor the provirus, although the latter population to a lesser extent. Proviral load increased with time, and inverse PCR analysis revealed the oligoclonal proliferation of infected cells. Although tax gene transcription was suppressed in human PBMC-NOG mice, it increased after in vitro culture. This result is similar to the phenotype of HTLV-I infected cells isolated from HTLV-I carriers. Furthermore, the reverse transcriptase inhibitors azidothymidine and tenofovir blocked primary infection in human PBMC-NOG mice. However, when tenofovir was administered 1 week after infection, the proviral loads did not differ from those of untreated mice, indicating that after initial infection, clonal proliferation of infected cells was predominant over de novo infection of previously uninfected cells. In this study, we demonstrate that the human PBMC-NOG mouse model should be a useful tool in studying the early stages of primary HTLV-I infection.

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