title: Estimating the fraction of progeny virions that must incorporate APOBEC3G for suppression of productive HIV-1 infection.
abstract: 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 ~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, R0, below unity. The fraction identified may serve as a quantitative guideline for strategies targeting the A3G-Vif axis.
authors.affiliation: Indian Institute of Science, Bangalore 560012, India.
authors.forename: Pulari U
authors.initials: PU
authors.lastname: Thangavelu
authors.affiliation: Indian Institute of Science, Bangalore 560012, India.
authors.forename: Vipul
authors.initials: V
authors.lastname: Gupta
authors.affiliation: Indian Institute of Science, Bangalore 560012, India. Electronic address: narendra@chemeng.iisc.ernet.in.
authors.forename: Narendra M
authors.initials: NM
authors.lastname: Dixit
mesh_terms: D000071480:APOBEC-3G Deaminase; D003564:Cytidine Deaminase / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D015658:HIV Infections / Q000201:enzymology* / Q000235:genetics / Q000821:virology; D015497:HIV-1 / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008962:Models, Theoretical; D011485:Protein Binding; D014771:Virion / Q000235:genetics / Q000502:physiology*; D014779:Virus Replication; D054320:vif Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism
chemical_list: D054320:vif Gene Products, Human Immunodeficiency Virus; C514847:vif protein, Human immunodeficiency virus 1; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase
keywords: APOBEC; Extinction threshold; Hypermutation; Mathematical model; Stochastic simulations; Vif; Viral dynamics