6th International AIDS Conference


San Francisco, California, USA — June 20-23, 1990

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Regulation of viral entry and syncytia formation in HIV-1 infected T-cell subclones by TNF alpha.

Int Conf AIDS 1990 Jun 20-23; 6:339 (abstract no. 1101)
Gruber M, Hewlett I, Simms T, Vujcic L, Manischewitz J, Golding H; FDA, CBER, Bethesda, Maryland, USA

OBJECTIVE: To study viral entry and HIV-1 induced cell fusion in subclones of CEM T cells treated with TNF alpha.

METHODS: CD4 positive subclones differing in CD4 expression and in HIV-1 infectibility were studied. CD4 surface density was determined by cytofluorometry. Viral entry was measured by appearance of proviral DNA templated shortly after viral exposure by quantitative polymerase chain reaction (PCR). The effect of TNF alpha treatment on HIV-1 infection was determined in syncytia formation assays (number/well) and measuring reverse transcriptase activity (cpm).

RESULTS: 1) Syncytia formation does not correlate with CD4 cell surface density. 2) Two CEM subclones, expressing high levels of CD4 are deficient in syncytia formation after HIV-1 infection. 3) The syncytia deficient clones contain lower amounts of proviral DNA than syncytia positive clones when analyzed shortly after HIV-1 exposure. 4) Pretreatment of syncytia positive clones with TNF alpha prior to viral infection enhances giant cell formation. 5) Formation of giant cells is induced in the syncytia deficient clones by adding TNF alpha 24h postinfection but not by TNF alpha pretreatment. 6) We will present evidence for a participation of TNF alpha in viral entry and formation of proviral DNA.

CONCLUSION: TNF alpha may play a multifunctional role in HIV-1 infection. In addition to its effect on virus transcription it may affect very early steps of viral entry.

Keywords: AEGIS, HIV-1, Giant Cells, T-Lymphocytes, Antigens, CD4, RNA-Directed DNA Polymerase, Tumor Necrosis Factor, Cell Fusion, Clone Cells, Polymerase Chain Reaction, Receptors, Tumor Necrosis Factor, virology, ICA6KWDaegis,hiv-1,giantcells,t-lymphocytes,antigens,cd4,rna-directeddnapolymerase,tumornecrosisfactor,cellfusion,clonecells,polymerasechainreaction,receptors,tumornecrosisfactor,virology,ica6

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