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

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