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

Autor(es)

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]

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: INFECTION GENETICS AND EVOLUTION; v. 78, MAR 2020.
• Citações Web of Science: 1

Resumo

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)

• Processo FAPESP: 11/12156-0 - Estudos das quasispecies do HIV com o uso de sequenciamento paralelo maciço
• Beneficiário: Ricardo Sobhie Diaz
• Modalidade de apoio: Auxílio à Pesquisa - Regular