Infection of human macrophages with an endogenous tumour necrosis factor- (TNF- )-independent human immunodeficiency virus type 1 isolate is unresponsive to the TNF- synthesis inhibitor RP 55778
| Autor: | Hervé Raoul, R. Le Naour, Dominique Dormont, Aloïse Mabondzo, Y. Henin, Anne Bousseau, Pascal Clayette |
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| Rok vydání: | 1994 |
| Předmět: |
Necrosis
Pyridines medicine.medical_treatment Gene Expression In Vitro Techniques Biology Virus Replication Virus Immunophenotyping Virology medicine Humans RNA Messenger Primary isolate Cells Cultured Interleukin-6 Tumor Necrosis Factor-alpha Macrophages virus diseases RNA-Directed DNA Polymerase HIV Reverse Transcriptase Reverse transcriptase Thiazoles Cytokine Viral replication Cell culture HIV-1 Tumor necrosis factor alpha medicine.symptom Interleukin-1 |
| Zdroj: | Journal of General Virology. 75:1379-1388 |
| ISSN: | 1465-2099 0022-1317 |
| Popis: | Monocyte-derived macrophages (MDM) were demonstrated to be susceptible to productive infection by the monocytotropic human immunodeficiency virus type 1 (HIV-1) strain HIV-1/Ba-L and by three primary HIV-1 isolates, HIV-1/DAS, HIV-1/PAR and HIV-1/THI. Production of tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and IL-1 beta was monitored between days 3 and 26 after MDM infection. TNF-alpha and IL-6 were detected in cell culture supernatants from days 16 to 21 following HIV-1/DAS, HIV-1/PAR and HIV-1/Ba-L infection, at the time of high viral replication. IL-1 beta was not found at the same time points. TNF-alpha mRNA expression occurred around the peak of both TNF-alpha levels and supernatant RT activities. In HIV-1/THI-infected macrophage cultures no endogenously produced TNF-alpha was observed, despite high levels of HIV-1 in MDM. This result demonstrates that a primary isolate may replicate independently of TNF-alpha in MDM. To investigate the relationship between TNF-alpha and viral replication we used a TNF-alpha synthesis inhibitor, RP 55778. Treatment throughout the course of cell culture resulted in a significant decrease in both TNF-alpha levels and viral production in HIV-1/DAS-, HIV-1/PAR- and HIV-1/Ba-L-infected MDM cultures. This phenomenon is reversed by adding recombinant human TNF-alpha to the RP 55778-treated cell cultures from day 14 post-infection. No effect of RP 55778 was observed in MDM cultures infected with the primary isolate HIV-1/THI, whose replication is independent of TNF-alpha production and therefore remained unchanged after RP 55778 treatment. We conclude that the clinical value of such a drug is directly dependent on the ability of the HIV-1 strains involved to induce TNF-alpha production at the time of viral replication. |
| Databáze: | OpenAIRE |
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