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| Author(s): |
Liã Bárbara Arruda
Total Authors: 1
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| Document type: | Master's Dissertation |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Instituto de Medicina Tropical de São Paulo (IMT) |
| Defense date: | 2010-05-17 |
| Examining board members: |
Jorge Simão do Rosário Casseb;
José Eduardo Levi;
Maria Cecilia Araripe Sucupira
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| Advisor: | Jorge Simão do Rosário Casseb |
| Abstract | |
The 35 amino acids of the V3-gp120 of HIV-1 env gene is the main determinant of viral tropism by the coreceptors CCR5 and CXCR4 used for HIV-1 cell entry. The development of antiretroviral strategies based on the coreceptor usage represents an important step to control the infection progression. However, the clinical application of CCR5 antagonists involves the coreceptor usage determination of viral strains in the infected individual. The bioinformatics predictive programs for coreceptor usage determination could be a more available alternative for screening candidates to receive CCR5 antagonists. This study aimed to employ bioinformatics tools to predict tropism and assess its applicability in clinical practice. Peripheral blood samples were collected from 101 individuals infected with HIV-1 and under clinical follow-up. DNA samples were extracted from PBMCs. The DNA samples were amplified by PCR and 94 V3 sequences were obtained. The predictive systems were evaluated using 185 sequences of known tropism from a database. This analysis provides the construction of an algorithm showing 94% of reliability. Thus, the 94 sample prediction showed a prevalence of 80% (n=75) of R5 strain and 20% (n=19) of X4 strain. The predictive systems could be an important strategy in the screening of the tropism. Nonetheless, they are not able to fully replace the coreceptor usage gold-standard assays. (AU) | |