Evidence of genomic information and structural restrictions of HIV-1 PR and RT gene regions from individuals experiencing antiretroviral virologic failure
| Autor: | Michelle Camargo, Ricardo Sobhie Diaz, Maria Cecília Araripe Sucupira, Rodrigo Sucupira Andrade Lima, Elidamar Nunes de Carvalho Lima, José Roberto Castilho Piqueira, Juliana Galinskas |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Microbiology (medical) Anti-HIV Agents 030106 microbiology Human immunodeficiency virus (HIV) HIV Infections Genome Viral Biology medicine.disease_cause Microbiology 03 medical and health sciences HIV Protease Drug Resistance Viral Genetics medicine Humans Treatment Failure Molecular Biology Gene Ecology Evolution Behavior and Systematics Resistance mutation Virology HIV Reverse Transcriptase VIROLOGIC FAILURE 030104 developmental biology Infectious Diseases Mutation Cohort HIV-1 Genomic information |
| Zdroj: | Infection, Genetics and Evolution. 78:104134 |
| ISSN: | 1567-1348 |
| DOI: | 10.1016/j.meegid.2019.104134 |
| Popis: | 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.For this purpose, we used genomic sequences from PR and RT of HIV-1 from a cohort of chronic patients followed up at São Paulo Hospital.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).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. |
| Databáze: | OpenAIRE |
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