Objectives: This study analyzed Protease-PR and Reverse Transcriptase-RT HIV-1 genomic information entropy metrics among patients under antiretroviral virologic failure, according to the numbers of virologic failures or resistance mutations.
Methods: For this purpose, we used genomic sequences from PR and RT of HIV-1 from a cohort of chronic patients followed up at Sao Paulo Hospital. Results: Informational entropy proportionally increases with the number of antiretroviral virologic failures in PR and RT (p < .001). Affected regions of PR were related to catalytic and structural functions, such as Fulcrum (K20) Flap (M46) and Cantilever (A71). In RT, this occurred at Fingers (E44) and Palm (K219). Informational entropy increases according to the number of resistance mutations in PR and RT (p < .001). Higher PR entropy was proportional to the resistance mutation numbers in Fulcrum (L10), Active site (L24) Flap (M46), Cantilever (L63) and near Interface (L90). In RT, they related to regions responsible for protein stability such as Fingers (T39) and Palm (L100). Conclusions: The antiretroviral selective pressure affects HIV genomic informational entropy at the PR and RT regions, leading to the emergence of more unstable virions. Mapping the three-dimensional structure in these HIV-1 proteins is relevant to designing new antiretroviral targeting resistant strains. Biography
Research Interests: My research line involves the analysis of genomic signatures evolution of molecules and specific sites and epitopes selection and recognition for development of vaccines efficiency and anti-HIV drugs. I´m very motivated and interested in various Science projects and research experiments. I´m currently working on projects that involves the genome viral evolution and nanotechnology to HIV vaccine at University of Sao Paulo and Infectious Diseases Division, Department of Medicine, Federal University of São Paulo in collaboration to Telecommunications and Control Engineering Department, Engineering School, both in Brazil.