Document 0617
 DOCN  M95A0617
 TI    Lymphocyte proliferation and HIV infection: in vitro examination of
       potential therapeutic strategies. American Pediatric Society 104th
       annual meeting and Society for Pediatric Research 63rd annual meeting;
       1994 May 2-5; Seattle.
 DT    9510
 AU    Krogstad P; Chen IS; Zack JA
 SO    Pediatr AIDS HIV Infect. 1994 Oct;5(5):319 (unnumbered abstract). Unique
       Identifier : AIDSLINE AIDS/95330427
 AB    Activation and proliferation of CD4 T-lymphocytes is required for
       productive infection of HIV. When quiescent T-lymphocytes are infected
       in vitro by HIV-1, the retroviral life-cycle is incomplete, due to
       failure to complete the reverse transcription process. Quiescent cells
       infected in this fashion harbor a labile replication intermediate which
       contains a partially reverse transcribed viral genome. Activation of
       cells containing this intermediate induces completion of reverse
       transcription and production of progeny virions. However, the active
       nature of this intermediate is extremely labile and rapidly degrades
       with time. Since > 90% of circulating T-lymphocytes in vivo are in the
       quiescent state, we have postulated that many of these cells may become
       infected and form partial reverse transcripts. These observations
       suggest therapeutic strategies based upon the limitation of lymphocyte
       proliferation, thus allowing intracellular degradation of these
       sub-viral HIV-1 particles. To test this hypothesis, we examined the
       ability of cyclosporin A, aphidicolin, and other inhibitors of
       lymphocyte proliferation to interfere with the reverse transcription
       process. We found that treatment of lymphocytes with inhibitors which
       interfered with cellular activation inhibited the completion of HIV-1
       reverse transcription. To examine the possibility that cellular
       activation influences reverse transcription by increasing available
       nucleotides, we examined reverse transcription in lymphocytes treated
       with hydroxyurea, a chemotherapeutic agent which decreases intracellular
       deoxynucleotide pools. At a concentration used for the treatment of
       malignancies, hydroxyurea limited cellular proliferation and virus
       production from lymphocytes infected in vitro. These data suggest
       possible therapeutic strategies for HIV-1 infection.
 DE    Aphidicolin/PHARMACOLOGY  Cyclosporine/PHARMACOLOGY  CD4-Positive
       T-Lymphocytes/IMMUNOLOGY/VIROLOGY  Human  Hydroxyurea/PHARMACOLOGY  HIV
       Infections/*IMMUNOLOGY  *HIV-1/GENETICS  In Vitro  *Lymphocyte
       Transformation/DRUG EFFECTS  Transcription, Genetic/DRUG EFFECTS
       MEETING ABSTRACT  JOURNAL ARTICLE

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