       Document 0381
 DOCN  M9620381
 TI    Selective infection of human T-lymphotropic virus type 1
       (HTLV-1)-infected cells by chimeric human immunodeficiency viruses
       containing HTLV-1 tax response elements in the long terminal repeat.
 DT    9602
 AU    Lin HC; Bodkin M; Lal RB; Rabson AB; Department of Molecular Genetics
       and Microbiology, Robert Wood; Johnson Medical School, University of
       Medicine and Dentistry of; New Jersey, Piscataway, USA.
 SO    J Virol. 1995 Nov;69(11):7216-25. Unique Identifier : AIDSLINE
       MED/96013826
 AB    Previous studies have suggested that the human immunodeficiency virus
       long terminal repeat (HIV LTR) enhancer/promoter sequences contribute to
       the replication ability of HIV in different T-cell lines; mutation of
       these sequences can alter HIV tropism. We have utilized site-specific
       mutagenesis to generate variants of HIV that exhibit specific tropism
       for human T-lymphotropic virus type 1 (HTLV-1) Tax-expressing CD4+ T
       cells. The wild-type HIV LTR NF-kappa B and Sp1 sites in an infectious
       molecular clone of HIV type 1 were replaced with sequences derived from
       the 21-bp Tax response elements (TRE) from the HTLV-1 LTR to generate
       TRE-containing chimeric HIVs (TRE-HIVs). The TRE-HIVs exhibit selective
       replication and cell killing in HTLV-infected human CD4+ T cells, but
       not in HTLV-negative T cells. Transient transfections suggested that
       Tax-TRE interactions could account for the observed replication
       specificity. The TRE-containing HIV LTRs were synergistically activated
       by the HIV Tat and HTLV-1 Tax transactivators. These results demonstrate
       that it is possible to specifically target HIV replication and
       cytotoxicity to HTLV-1+, CD4+ human T cells, on the basis of Tax-TRE
       interactions, and provide a model for the development of specific,
       cytotoxic, retroviral gene therapy vectors for HTLV-1-infected cells
       based on alterations of the LTR transcriptional regulatory elements.
       They also suggest that HIV Tat can cooperate with heterologous
       transcriptional activators, such as Tax, which act through upstream
       binding sites without directly binding to DNA.
 DE    Base Sequence  Cell Line  Cell Survival  Chimera  Chloramphenicol
       Acetyltransferase/BIOSYNTHESIS  CD4-Positive T-Lymphocytes  Gene
       Products, tat/BIOSYNTHESIS/*METABOLISM  Gene Products,
       tax/BIOSYNTHESIS/GENETICS/*METABOLISM  Human  HIV/GENETICS/*PHYSIOLOGY
       *HIV Long Terminal Repeat  HTLV-I/*GENETICS/*PHYSIOLOGY  Kinetics
       Molecular Sequence Data  Plasmids  Recombinant Fusion
       Proteins/BIOSYNTHESIS  *Regulatory Sequences, Nucleic Acid  *Repetitive
       Sequences, Nucleic Acid  Restriction Mapping  Support, Non-U.S. Gov't
       Support, U.S. Gov't, P.H.S.  Transfection  *Virus Replication  JOURNAL
       ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

