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M94A0637.TXT
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1994-10-21
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Document 0637
DOCN M94A0637
TI Molecular mechanisms of interleukin 4 stimulation of HIV mRNA expression
in human monocytes.
DT 9412
AU Naif H; Mathijs JM; Shon MH; Chang J; Cunningham T; Virology Department,
Westmead Hospital, National Centre in HIV; Research, Sydney, Australia.
SO Annu Conf Australas Soc HIV Med. 1993 Oct 28-30;5:65 (abstract no. TB7).
Unique Identifier : AIDSLINE ASHM5/94349018
AB HIV-1 can productively infect mononuclear phagocytes derived from blood
bone marrow, brain and lung. Interleukin 4 (IL-4) and tumor necrosis
factor alpha (TNF alpha) have previously been shown to stimulate HIV
replication in monocytes and macrophages (1,2). The mechanism of IL-4
stimulation was investigated and compared with the known effects of TNF
alpha. Interleukin 4 (IL-4) upregulated the expression of HIV mRNA
within the first two days after inoculation of purified human monocytes
and U937 cells also upregulated production of HIV RNA but to a greater
degree than IL-4 and reaching a peak 3-4 days after inoculation in both
cell types. However, there was no synergistic stimulation of HIV mRNA
replication when IL-4 and TNF-alpha were combined. Northern blots showed
an increase in genomic and spliced RNAs at these times. The effects of
these cytokines on 2 and 4kb spliced RNA in the first 24 hours are
currently being studied. Using nuclear run-on assays, upregulation of
HIV expression induced by IL-4 in infected monocytes within 24 hours was
shown to occur at the transcriptional level, with 2-3 fold increase in
HIV mRNA expression compared to the unstimulated infected cells. The
kinetics of enhancement of NFkB nuclear translocation and binding by
IL-4 and TNF-a correlated respectively with the kinetics of enhancement
of HIV-RNA expression.
DE Cell Line Gene Expression Regulation, Viral/PHYSIOLOGY Human
HIV-1/*GENETICS Interleukin-4/*PHYSIOLOGY Monocytes/*MICROBIOLOGY
RNA, Messenger/*GENETICS Tumor Necrosis Factor/PHYSIOLOGY
Up-Regulation (Physiology)/PHYSIOLOGY MEETING ABSTRACT
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).