PMTI, a broadly active unusual single-stranded polyribonucleotide, inhibits human immunodeficiency virus replication by multiple mechanisms
| Autor: | Larry J. Ross, M J Snow, Vijai K. Agrawal, Arthur D. Broom, White El, Carol Lackman-Smith, Susan M. Halliday, Robert W. Buckheit |
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| Rok vydání: | 1999 |
| Předmět: |
0301 basic medicine
Anti-HIV Agents viruses medicine.medical_treatment 030106 microbiology HIV Infections Biology Virus Replication 01 natural sciences Virus 03 medical and health sciences Viral entry medicine Tumor Cells Cultured Humans RNase H Protease virus diseases General Medicine Thionucleotides Nucleotidyltransferase Virology Molecular biology Reverse transcriptase HIV Reverse Transcriptase 0104 chemical sciences Integrase 010404 medicinal & biomolecular chemistry Viral replication Poly I biology.protein HIV-1 Reverse Transcriptase Inhibitors HeLa Cells |
| Zdroj: | Antiviral chemistrychemotherapy. 10(1) |
| ISSN: | 0956-3202 |
| Popis: | Poly(1-methyl-6-thioinosinic acid), or PMTI, is a single-stranded polyribonucleotide and is the first homopolyribonucleotide devoid of Watson—Crick hydrogen bonding sites to show potent human immunodeficiency virus (HIV) inhibition. PMTI was found to be active when evaluated against a variety of low passage clinical HIV isolates in fresh human peripheral blood cells, including T cell-tropic and monocyte—macrophage-tropic viruses, syncytium-inducing and non-syncytium-inducing viruses and viruses representative of the various HIV-1 clades (A through F). The compound was active against HIV-2, all nucleoside and non-nucleoside reverse transcriptase (RT) inhibitor drug-resistant virus isolates tested and interacted with AZT or ddI to synergistically inhibit HIV infection. In biochemical inhibition assays, PMTI was determined to be a potent inhibitor of HIV-1 and HIV-2 RT, including RTs with mutations that engender resistance to nucleoside and non-nucleoside RT inhibitors. PMTI inhibited both the polymerase and RNase H activities of HIV RT. PMTI did not inhibit HIV-1 protease or integrase. Cell-based mechanism of action assays indicated that PMTI also interfered with early events in the entry of HIV into target cells. Furthermore, PMTI inhibited the fusion of gp120-expressing and CD4-expressing cells, but at concentrations approximately 1 log10 greater than those that inhibited virus entry. These results suggest that the homopolyribonucleotide PMTI blocks HIV replication in human cells at its earliest stages by multiple mechanisms, inhibition of virus entry and inhibition of RT. |
| Databáze: | OpenAIRE |
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