PMID- 10694813
OWN - NLM
STAT- MEDLINE
DCOM- 20000316
LR  - 20121115
IS  - 0969-7128 (Print)
IS  - 0969-7128 (Linking)
VI  - 7
IP  - 4
DP  - 2000 Feb
TI  - Inhibition of HIV-1 replication in chronically infected cell lines and peripheral 
      blood mononuclear cells by retrovirus-mediated antitat gene transfer.
PG  - 321-8
AB  - Among potential genetic targets for intervention in the HIV-1 life cycle, the tat 
      gene product is a key target. We investigated the ability of an antitat gene to 
      inhibit HIV-1 activation and replication in chronically infected promonocyte (U1) 
      and T cell (ACH-2) lines in vitro. U1 and ACH-2 cells were transduced with an 
      antitat gene expressing RNA with dual (polymeric Tat activation response element 
      and antisense-tat) function that interferes with HIV-1 replication. Tumor 
      necrosis factor-alpha (TNF-alpha) plus phorbol 12- myristate 13-acetate 
      (PMA)-induced HIV-1 expression, as determined by reverse transcribed PCR and 
      reverse transcriptase (RT) assays, was significantly inhibited in U1 and ACH-2 
      cells transduced with the antitat gene, compared with the cells transduced with 
      control vector and untransduced cells. This resistance to TNF-alpha plus 
      PMA-induced HIV-1 expression was demonstrated in antitat gene-transduced U1 and 
      ACH-2 cells maintained in G418-free media for 5 months, suggesting that 
      functional antitat gene may persist for many months in transduced cells and their 
      progeny. Most importantly, we demonstrate that the antitat gene, when introduced 
      into peripheral blood mononuclear cells (PBMC) isolated from patients with HIV-1 
      infection, inhibited TNF-alpha plus PMA-induced viral replication as determined 
      by RT-PCR and RT activity. In addition, the antitat gene enhanced the survival of 
      CD4+ T lymphocytes from such patients. These data suggest the feasibility of 
      utilizing antitat gene therapy to block activation and replication of HIV-1 in 
      latently infected monocytes and T- lymphocytes in vivo. Gene Therapy (2000) 7, 
      321-328.
FAU - Li, Y
AU  - Li Y
AD  - Division of Immunologic and Infectious Diseases, Joseph Stokes Jr Research 
      Institute of The Children's Hospital of Philadelphia, Department of Pediatrics, 
      University of Pennsylvania Medical School, Philadelphia, PA 19104, USA.
FAU - Starr, S E
AU  - Starr SE
FAU - Lisziewicz, J
AU  - Lisziewicz J
FAU - Ho, W Z
AU  - Ho WZ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Gene Ther
JT  - Gene therapy
JID - 9421525
SB  - IM
MH  - Cell Line
MH  - Flow Cytometry
MH  - Gene Expression
MH  - Genes, tat/*genetics
MH  - Genetic Therapy/methods
MH  - HIV Infections/therapy
MH  - HIV-1/*genetics
MH  - Humans
MH  - Leukocytes, Mononuclear/virology
MH  - Reverse Transcriptase Polymerase Chain Reaction/methods
MH  - Transduction, Genetic/genetics
MH  - Virus Activation
MH  - Virus Replication/*genetics
EDAT- 2000/03/01 09:00
MHDA- 2000/03/18 09:00
CRDT- 2000/03/01 09:00
PHST- 2000/03/01 09:00 [pubmed]
PHST- 2000/03/18 09:00 [medline]
PHST- 2000/03/01 09:00 [entrez]
AID - 10.1038/sj.gt.3301088 [doi]
PST - ppublish
SO  - Gene Ther. 2000 Feb;7(4):321-8. doi: 10.1038/sj.gt.3301088.