test_moissonnage_selune
type: Agent

Role of HIV-1 accessory proteins Vif and Vpr in drug resistance in patients failing antiretroviral treatment
type: Dataset
contact point: Organization
  fn: CCSD
keyword: theses
keyword: antiretroviral-resistance
keyword: resistance-aux-antiretroviraux
keyword: infoeu-reposemanticsdoctoralthesis
keyword: variabilite-genetique
keyword: rilpivirine
keyword: vih-1
keyword: vif
keyword: didanosine
keyword: sdvmpvirlife-sciences-q-biomicrobiology-and-parasitologyvirology
keyword: vpr
keyword: hiv-1
keyword: genetic-variability
landing page: https://theses.hal.science/tel-00829510
description: HIV-1 Vif and Vpr proteins may play a role in viral genetic variability. Indeed, Vpr limits error-induced mutations by the viral reverse transcriptase by recruiting the nuclear form of Uracil DNA glycosylase (UNG2). On the other hand, Vif prevents APOBEC3-induced hypermutation on the viral genome. Genetic variability induced by these HIV accessory proteins might play a role in the appearance of drug resistance associated mutations. We first identified a mutation in vif (K22H) frequently found in patients failing antiretroviral treatment. Biochemical studies and viral replication kinetics demonstrated that this mutation favor the appearance of G-to-A mutations in proviral DNA (as a result of partial activity against APOBEC3G). K22H mutation led to the emergence of the drug resistance mutation M184I in the reverse transcriptase (RT) gene. In another study, we showed that E138K and M184I mutations in RT (often co-selected in patients failing emtricitabine/tenofovir/rilpivirine) concomitantly appear as a result of APOBEC3 editing in the absence of drug exposure, thus providing a new key towards understanding mechanisms of escape of this new drug combination. In a third study, we identified a mutation in vpr (E17A) associated to "thymidin analog mutations" TAMs (M41L, L210W, T215Y in RT) in patients failing HAART. Phenotypic assays demonstrated that viruses harboring E17A+TAMs conferred higher resistance to didanosine than virus harboring TAMs or E17A alone. This study highlights a novel role of Vpr in HIV drug resistance.
identifier: NNT: 2012PAO66188
issued: 2026-05-10T21:40:41.647050
language: fr
modified: 2026-05-10T21:40:41.647055

Role of HIV-1 accessory proteins Vif and Vpr in drug resistance in patients failing antiretroviral treatment
type: Distribution
access URL: https://theses.hal.science/tel-00829510
format: HTML
issued: 2026-05-10T21:40:41.653928
modified: 2026-05-10T21:40:41.632218