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M94A0745.TXT
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1994-10-21
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Document 0745
DOCN M94A0745
TI Lack of inhibition of HIV replication in chronically infected
macrophages by Tat inhibitors Ro-5-3335 and Ro-24-7429.
DT 9412
AU Dunne A; Siregar H; Sonza S; Crowe S; Macfarlane Burnet Centre for
Medical Research, Fairfield; Hospital, Vic.
SO Annu Conf Australas Soc HIV Med. 1993 Oct 28-30;5:100 (poster no. 51).
Unique Identifier : AIDSLINE ASHM5/94348910
AB OBJECTIVE: HIV infects different cell types including CD4+ lymphocytes
and monocyte/macrophages (Mphi). We have examined the effect of the Tat
inhibitors Ro-5-3335 and Ro-24-7429 in cultured human peripheral Mphi.
METHODS: MO were isolated from HIV seronegative donors by gradient
centrifugation and plastic adherence. Cells were infected with HIV Ba-L
for 3 hours (acute infection) or 14 days (chronic infection) prior to
addition of drug. Inhibition of HIV replication by each drug was
assessed by quantitation of HIV p24 in supernatant and HIV RNA analysis.
RESULTS: Ro-5-3335 (10 microM) and Ro-24-7429 (10 microM) resulted in
73-80% and 92-100% inhibition respectively of acute infection with a
clear dose response curve; chronically infected Mphi were less
susceptible to these drugs with both compounds at 10 microM having < 50%
inhibitory effect. RNA slot blot analysis of acutely infected Mphi
showed inhibition of HIV mRNA by Ro-24-7429 at a concentration of 10
microM. Viability of cells at tested concentrations was > 90%.
CONCLUSION: The Tat inhibitors were effective in inhibiting acute HIV
infection in Mphi but not in chronically infected cells, findings which
differ from published studies using T cell lines. Comparative studies
are underway to investigate the effect of these compounds in acutely and
chronically infected T cell lines.
DE Antiviral Agents/*PHARMACOLOGY Benzodiazepines/*PHARMACOLOGY
Benzodiazepinones/*PHARMACOLOGY Cells, Cultured Gene Products,
tat/*ANTAGONISTS & INHIB Human HIV/*DRUG EFFECTS
Macrophages/*MICROBIOLOGY Pyrroles/*PHARMACOLOGY Virus
Replication/*DRUG EFFECTS MEETING ABSTRACT
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).