CCR5 density levels on primary CD4 T cells impact the replication and Enfuvirtide susceptibility of R5 HIV-1
| Autor: | Alonso Heredia, Douty Bamba, Nhut Le, Bruce L. Gilliam, Robert C. Gallo, Robert R. Redfield, George K. Lewis, Robin Flinko, Anthony L. DeVico |
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| Rok vydání: | 2007 |
| Předmět: |
CD4-Positive T-Lymphocytes
Enfuvirtide Receptors CCR5 viruses Immunology Virus Replication Virus Cell Line HIV Fusion Inhibitors medicine Humans Immunology and Allergy Receptor Cells Cultured Infectivity biology virus diseases T lymphocyte biology.organism_classification Virology HIV Envelope Protein gp41 Peptide Fragments Infectious Diseases Viral replication Cell culture Lentivirus HIV-1 medicine.drug |
| Zdroj: | AIDS. 21:1317-1322 |
| ISSN: | 0269-9370 |
| DOI: | 10.1097/qad.0b013e32815278ea |
| Popis: | Objective and design Studies in cell lines have demonstrated that CCR5 coreceptor levels influence the replication efficiency and Enfuvirtide (T-20) susceptibility of R5 HIV-1 strains. At present, however, the role that CCR5 levels on primary CD4 T cells--which are markedly lower than in cell lines and vary only approximately fivefold among most donors--may play in virus replication levels or susceptibility to T-20 is not known. In the present study we evaluated the impact of differences in CCR5 levels among donor CD4 T cells on the infection efficiency and T-20 susceptibility of R5 HIV-1. Methods CD4 and CCR5 density levels were determined by Quantitative FACS analysis. Virus infectivity assays were conducted in cell lines and primary cells. Associations between coreceptor density, virus replication and T-20 sensitivity were tested using the Spearman's correlation test. Results We found a positive correlation (r, 0.55; P = 0.011) between CCR5 density levels on primary CD4 T cells and replication of R5 HIV-1. In cell lines expressing physiologically relevant levels of CD4 and CCR5, T-20 was significantly more potent in cells with low CCR5 levels. In addition, T20 50% inhibitory concentrations for R5 HIV-1 replication varied approximately 100-fold among primary cells from different donors and they were positively correlated with CCR5 density values (r, 0.84; P = 0.00004). Conclusions These results suggest that CCR5 density levels in HIV-1 patients may impact the activity of T-20 against R5 strains and that therapeutic approaches to alter CCR5 density may potentiate T-20. |
| Databáze: | OpenAIRE |
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