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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Evidence of genomic information and structural restrictions of HIV-1 PR and RT gene regions from individuals experiencing antiretroviral virologic failure

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de Carvalho Lima, Elidamar Nunes [1, 2] ; Andrade Lima, Rodrigo Sucupira [2] ; Castilho Piqueira, Jose Roberto [2] ; Cecilia Sucupira, Maria [1] ; Camargo, Michelle [1] ; Galinskas, Juliana [1] ; Diaz, Ricardo Sobhie [1]
Total Authors: 7
[1] Univ Fed Sao Paulo, Dept Med, Infect Dis Div, Sao Paulo - Brazil
[2] Univ Sao Paulo, Engn Sch, Telecommun & Control Engn Dept, Sao Paulo - Brazil
Total Affiliations: 2
Document type: Journal article
Web of Science Citations: 0

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. (AU)

FAPESP's process: 11/12156-0 - HIV quasispecies studies using ultra-deep sequencing
Grantee:Ricardo Sobhie Diaz
Support type: Regular Research Grants