Estimating the fraction of progeny virions that must incorporate APOBEC3G for suppression of productive HIV-1 infection
| Autor: | Vipul Gupta, Narendra M. Dixit, Pulari U. Thangavelu |
|---|---|
| Jazyk: | angličtina |
| Předmět: |
viruses
Human immunodeficiency virus (HIV) Down-Regulation HIV Infections APOBEC-3G Deaminase Biology medicine.disease_cause Virus Replication Mathematical model Virology Cytidine Deaminase medicine vif Gene Products Human Immunodeficiency Virus Humans Fraction (mathematics) Extinction threshold APOBEC3G Host factor Stochastic simulations Hypermutation Virion APOBEC Chemical Engineering Models Theoretical Stop codon Vif Viral dynamics HIV-1 Basic reproduction number Protein Binding |
| Zdroj: | Virology. :224-228 |
| ISSN: | 0042-6822 |
| DOI: | 10.1016/j.virol.2013.11.026 |
| Popis: | The contest between the host factor APOBEC3G (A3G) and the HIV-1 protein Vif presents an attractive target of intervention. The extent to which the A3G-Vif interaction must be suppressed to tilt the balance in favor of A3G remains unknown. We employed stochastic simulations and mathematical modeling of the within-host dynamics and evolution of HIV-1 to estimate the fraction of progeny virions that must incorporate A3G to render productive infection unsustainable. Using three different approaches, we found consistently that a transition from sustained infection to suppression of productive infection occurred when the latter fraction exceeded similar to 0.8. The transition was triggered by A3G-induced hypermutations that led to premature stop codons compromising viral production and was consistent with driving the basic reproductive number, R-o, below unity. The fraction identified may serve as a quantitative guideline for strategies targeting the A3G-Vif axis. (C) 2013 Elsevier Inc. All rights reserved. |
| Databáze: | OpenAIRE |
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