De novo human T-cell leukemia virus type 1 infection of human lymphocytes in NOD-SCID, common γ-chain knockout mice

被引:42
作者
Miyazato, Paola
Yasunaga, Jun-ichirou
Taniguchi, Yuko
Koyanagi, Yoshio
Mitsuya, Hiroaki
Matsuoka, Masao
机构
[1] Kyoto Univ, Inst Virus Res, Lab Virus Immunol, Sakyo Ku, Kyoto 6068507, Japan
[2] Kyoto Univ, Inst Virus Res, Lab Virus Pathogenesis, Kyoto 6068507, Japan
[3] Kumamoto Univ, Grad Sch Med, Dept Hematol, Kumamoto 8608556, Japan
[4] Kumamoto Univ, Grad Sch Med, Dept Infect Dis, Kumamoto 8608556, Japan
关键词
D O I
10.1128/JVI.01009-06
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Human T-cell leukemia virus type 1 (HTLV-1) is the etiologic agent of adult T-cell leukemia, a disease that is triggered after a long latency period. HTLV-1 is known to spread through cell-to-cell contact. In an attempt to study the events in early stages of HTLV-1 infection, we inoculated uninfected human peripheral blood mononuclear cells and the HTLV-1-producing cell line MT-2 into NOD-SCID, common gamma-chain knockout mice (human PBMC-NOG mice). HTLV-1 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 harbored provirus to a lesser extent. Proviral loads increased with time, and inverse PCR analysis revealed the oligocional proliferation of infected cells. Although tax gene transcription was suppressed in human PBMC-NOG mice, it increased after in vitro culture. This is similar to the phenotype of HTLV-1-infected cells isolated from HTLV-1 carriers. Furthermore, the reverse transcriptase inhibitors azidothymidine and tenofovir blocked primary infection in human PBMC-NOG mice. However, when tenofovir was administered I 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 demonstrated that the human PBMC-NOG mouse model should be a useful tool in studying the early stages of primary HTLV-1 infection.
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页码:10683 / 10691
页数:9
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