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M9490498.TXT
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1994-09-24
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Document 0498
DOCN M9490498
TI Effect of 3'-azido-3'-deoxythymidine and 2',3'-dideoxyinosine on
establishment of human immunodeficiency virus type 1 infection in
cultured CD8+ lymphocytes.
DT 9411
AU Mercure L; Brenner BJ; Phaneuf D; Tsoukas C; Wainberg MA; Lady Davis
Institute, Jewish General Hospital, Montreal, Quebec,; Canada.
SO Antimicrob Agents Chemother. 1994 May;38(5):986-90. Unique Identifier :
AIDSLINE MED/94346852
AB Several groups have shown that peripheral CD8+ lymphocytes can be
infected with human immunodeficiency virus type 1 (HIV-1), resulting in
noncytopathic infection and persistent production of viral particles. We
studied the ability of 3'-azido-3'-deoxythymidine (AZT) and
2',3'-dideoxyinosine (ddI) to inhibit the establishment of HIV-1
infection in CD8+ cells that were derived from cultures of peripheral
blood lymphocytes exposed to both virus and drug. In situ infection of
CD8+ cells was demonstrated by double flow cytometry analysis by using
both anti-glycoprotein 120 (anti-gp120) and anti-CD8 monoclonal
antibodies. At higher concentrations of drug (e.g., 0.4 microM AZT), the
production of viral particles was inhibited for over 2 months, as
assessed by p24 antigen levels in the culture medium. We also performed
a time course experiment to determine whether HIV-1 infection of CD8+
cells would be affected by treatment of peripheral blood lymphocytes
with AZT or ddI for different intervals following exposure to virus.
Quantitative PCR revealed that 0.4 microM AZT, added as late as 24 h
after infection, interfered with the formation of proviral DNA in CD8+
cells. Both HIV-1 load and the production of progeny virions by CD8+
cells, as monitored by reverse transcriptase activity in culture fluids,
were inhibited by both AZT and ddI in a dose-dependent manner.
DE Antibodies, Monoclonal/IMMUNOLOGY Antigens, CD8/*IMMUNOLOGY Base
Sequence Cells, Cultured Didanosine/*PHARMACOLOGY DNA Probes DNA,
Viral/ANALYSIS Flow Cytometry Human HIV Infections/*DRUG
THERAPY/MICROBIOLOGY *HIV-1 Lymphocytes/DRUG
EFFECTS/IMMUNOLOGY/*MICROBIOLOGY Molecular Sequence Data Support,
Non-U.S. Gov't Zidovudine/*PHARMACOLOGY JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).