| Autor: |
Miyauchi K; AIDS Research Center, National Institute of Infectious Diseases, Toyama, Shinjuku, Tokyo, Japan., Komano J, Myint L, Futahashi Y, Urano E, Matsuda Z, Chiba T, Miura H, Sugiura W, Yamamoto N |
| Jazyk: |
angličtina |
| Zdroj: |
Antiviral chemistry & chemotherapy [Antivir Chem Chemother] 2006; Vol. 17 (4), pp. 167-74. |
| DOI: |
10.1177/095632020601700401 |
| Abstrakt: |
Here we report that sparsomycin, a streptococcal metabolite, enhances the replication of HIV-1 in multiple human T cell lines at a concentration of 400 nM. In addition to wild-type HIV-1, sparsomycin also accelerated the replication of low-fitness, drug-resistant mutants carrying either D30N or L90M within HIV-1 protease, which are frequently found mutations in HIV-1-infected patients on highly active antiretroviral therapy (HAART). Of particular interest was that replication enhancement appeared profound when HIV-1 such as the L90M-carrying mutant displayed relatively slower replication kinetics. The presence of sparsomycin did not immediately select the fast-replicating HIV-1 mutants in culture. In addition, sparsomycin did not alter the 50% inhibitory concentration (IC50) of antiretroviral drugs directed against HIV-1 including nucleoside reverse transcriptase inhibitors (lamivudine and stavudine), non-nucleoside reverse transcriptase inhibitor (nevirapine) and protease inhibitors (nelfinavir, amprenavir and indinavir). The IC50s of both zidovudine and lopinavir against multidrug resistant HIV-1 in the presence of sparsomycin were similar to those in the absence of sparsomycin. The frameshift reporter assay and Western blot analysis revealed that the replication-boosting effect was partly due to the sparsomycin's ability to increase the -1 frameshift efficiency required to produce the Gag-Pol transcript. In conclusion, the use of sparsomycin should be able to facilitate the drug resistance profiling of the clinical isolates and the study on the low-fitness viruses. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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