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).