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

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2591-2596
Number of pages6
JournalBlood
Volume84
Issue number8
Publication statusPublished - Oct 15 1994
Externally publishedYes

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T-cells
Cell growth
Retroviridae
Taxation
Viruses
T-Lymphocytes
Adult T Cell Leukemia Lymphoma
Growth
Thymidine Kinase
Simplexvirus
Acyclovir
Terminal Repeat Sequences
Gene therapy
Genetic Therapy
tax Gene Products
Cell Line
Poisons
Viral Proteins
Nucleosides
Phosphorylation

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Selective inhibition of human T-lymphotropic virus type I-transformed human T-cell growth by a tax-targeted conditionally cytotoxic recombinant retrovirus. / Fujita, Masatoshi; Murata, Ken; Shiku, Hiroshi.

In: Blood, Vol. 84, No. 8, 15.10.1994, p. 2591-2596.

Research output: Contribution to journalArticle

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