Effect of 3'-azido-3'-deoxythymidine on human immunodeficiency virus type 1 replication in human fetal brain macrophages
| Autor: | Eric J. Arts, R Geleziunas, H Goldman, Mark A. Wainberg, F Boulerice |
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| Rok vydání: | 1993 |
| Předmět: |
Time Factors
viruses HIV Core Protein p24 Clone (cell biology) Biology Virus Replication Antiviral Agents Virus Zalcitabine chemistry.chemical_compound Zidovudine Fetus medicine Humans Macrophage Pharmacology (medical) RNA Messenger Cells Cultured Pharmacology Acquired Immunodeficiency Syndrome Nucleoside analogue Macrophages Brain virus diseases Stereoisomerism Virology Infectious Diseases chemistry Viral replication Lamivudine DNA Viral HIV-1 DNA Research Article medicine.drug |
| Zdroj: | Antimicrobial Agents and Chemotherapy. 37:1305-1312 |
| ISSN: | 1098-6596 0066-4804 |
| DOI: | 10.1128/aac.37.6.1305 |
| Popis: | We investigated whether cells derived from the fetal central nervous system can support productive infection by a human immunodeficiency virus type 1 (HIV-1) isolate termed UHC-1, produced by a cellular clone derived from HIV-1 strain HIV-IIIB chronically infected U-937 promonocytic cells, and what the effect of nucleoside analogs might be on viral replication in this system. Fractionation of human fetal brain tissue into two different populations, enriched for either astrocytes or macrophages, showed that only the latter were able to support productive UHC-1 replication and generation of detectable progeny virus. Pretreatment of fetal brain macrophages with either of two nucleoside analogs, 3'-azido-3'-deoxythymidine (AZT) or the (-) enantiomer of 2'-deoxy-3'-thiacytidine, efficiently blocked production of progeny virus. Generation of unintegrated proviral DNA and HIV-1 transcripts were inhibited by pretreatment of fetal brain macrophages with 1 microM AZT. Administration of AZT at 24 h postinfection led to a slight reduction in viral transcript levels and viral progeny production by day 15 postinfection; however, brain macrophages under these conditions did not contain detectable amounts of unintegrated viral DNA. These results suggest that AZT may interfere with the accumulation of unintegrated HIV-1 DNA in brain macrophages. This is the first demonstration that nucleoside analogs are able to block HIV-1 replication in primary cultures of brain cells. |
| Databáze: | OpenAIRE |
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