Selective inhibition of human T-lymphotropic virus type I-transformed human T-cell growth by a tax-targeted conditionally cytotoxic recombinant retrovirus

Masatoshi Fujita, Ken Murata, Hiroshi Shiku

研究成果: Contribution to journalArticle査読

10 被引用数 (Scopus)

抄録

Adult T-cell leukemia (ATL), a disorder associated with high mortality rates, arises from human T-lymphotropic virus type I (HTLV-I)-infected CD4+ T cells. We designed a retroviral vector-based gene therapy approach to ATL. The long terminal repeat (LTR) of HTLV-I is transactivated by the viral tax protein. We constructed a hybrid gene consisting of herpes simplex virus thymidine kinase (HSV TK) under the control of the HTLV-I LTR and inserted it into a retroviral vector. When HTLV-I-transformed and tax-expressing human T- cell lines were infected with this recombinant retrovirus (LNLTKα virus), they expressed high levels of HSV TK and exhibited increased sensitivity to acyclovir, a nucleoside analog that is converted to the toxic anabolite after phosphorylation by the HSV TK. On the other hand, the retroviral infection had little effect on acyclovir-induced cytotoxicity in HTLV-I-negative human hematopoietic cell lines. Our data may provide the prospect of the gene therapy for ATL by tax-targeted selective elimination of leukemic cells.

本文言語英語
ページ(範囲)2591-2596
ページ数6
ジャーナルBlood
84
8
DOI
出版ステータス出版済み - 10 15 1994
外部発表はい

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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