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. 1993 Jun;67(6):3569–3575. doi: 10.1128/jvi.67.6.3569-3575.1993

Release of human immunodeficiency virus by THP-1 cells and human macrophages is regulated by cellular adherence and activation.

R J Shattock 1, J S Friedland 1, G E Griffin 1
PMCID: PMC237704  PMID: 7684470

Abstract

Macrophage adherence, an important regulatory signal, has the potential to affect human immunodeficiency virus (HIV) production either directly or by priming monocytes to respond to other activating signals. We have investigated the role of adherence as an activator of HIV-1 transcription and release. The effects of adherence on HIV-1 transcription were examined by using THP-1 cells, a human monocytic cell line, transfected with HIV long terminal repeat (LTR)-chloramphenicol acetyltransferase (CAT) constructs. The effects of adherence on release of HIV-1 were investigated in both HIV-1-infected THP-1 cells and human peripheral blood monocyte-derived macrophages (MDM). Adherence of lipopolysaccharide (LPS)-stimulated THP-1 cells to either tissue culture plastic or endothelial cells was crucial for enhanced HIV-1 transcription as measured by LTR-CAT expression. Such increased LTR-CAT expression did not occur with an HIV LTR construct containing mutated NF-kappa B binding sites. In contrast, release of whole HIV, measured by reverse transcriptase (RT) activity in tissue culture medium, was reduced upon adherence of stimulated HIV-1-infected THP-1 cells without suppression of HIV LTR-CAT transcription or p24 release. This finding suggested that activation of adherent monocytic cells interfered with HIV assembly and release. Although the reduction of RT activity following activation of HIV-1-infected MDM was independent of adhesion, adherence alone of nonstimulated HIV-infected MDM to endothelial cells was sufficient to induce a reduction in RT release. This study demonstrates that LPS stimulation of monocytic cells enhances HIV LTR transcription under adherent conditions. In contrast, activation of adherent monocytic cells infected with HIV reduced viral release.

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Selected References

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