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M9490673.TXT
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1994-09-24
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Document 0673
DOCN M9490673
TI Inhibition of HIV-1 multiplication in a human CD4+ lymphocytic cell line
expressing antisense and sense RNA molecules containing HIV-1 packaging
signal and Rev response element(s).
DT 9411
AU Cohli H; Fan B; Joshi RL; Ramezani A; Li X; Joshi S; Department of
Microbiology, University of Toronto, Ontario,; Canada.
SO Antisense Res Dev. 1994 Spring;4(1):19-26. Unique Identifier : AIDSLINE
MED/94339688
AB Moloney murine leukemia virua (MoMuLV)-derived retroviral vectors were
engineered to express human immunodeficiency virus type 1 (HIV-1)
packaging (psi) signal and Rev response element (RRE) sequences in
either sense or antisense orientation. The RRE sequences were expressed
under the control of the herpes simplex virus (HSV) thymidine kinase
(tk) promoter fused to the HIV-1 trans-activation-responsive (TAR)
element, while the psi signal sequences were expressed under control of
the HSV tk promoter. Both RRE and psi signal sequences were expressed as
part of the 3' untranslated region of the neomycin phosphotransferase
(neo) mRNA. The constructs were used to transfect/infect packaging cell
lines and the retroviral vector particles released were used to infect a
human CD4+ lymphocyte-derived MT4 cell line. The stable MT4
transformants, harboring proviral vector DNA expressing one to two
copies of HIV-1 RRE and psi signal in either antisense or sense
orientation, were each tested for their susceptibility to HIV-1
infection. Compared to the results obtained with the control cells
lacking any of the test DNA sequences, the rate of HIV-1 production
remained unaltered in RRE1+ (sense RNA containing a single copy of RRE)
RNA-containing cells, whereas it was delayed in cells expressing both
RRE2+ (sense RNA containing two copies of RRE) and RRE1- (antisense RNA
containing a single copy of RRE) RNA-expressing cells. In cells
expressing HIV-1 psi signal, HIV-1 production remained unaltered in psi
+ RNA-expressing cells, whereas it was delayed by up to 30 days in psi -
RNA-expressing cells.(ABSTRACT TRUNCATED AT 250 WORDS)
DE Base Sequence Cell Line Genes, env/*GENETICS Genetic Vectors Human
HIV-1/GENETICS/*PHYSIOLOGY Molecular Sequence Data Plasmids
Polymerase Chain Reaction Promoter Regions (Genetics) Regulatory
Sequences, Nucleic Acid/*GENETICS RNA, Antisense/*GENETICS RNA,
Viral/*GENETICS Support, Non-U.S. Gov't Transfection T4
Lymphocytes/*MICROBIOLOGY Virus Replication JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).