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Estimating the fraction of progeny virions that must incorporate APOBEC3G for suppression of productive HIV-1 infection

Thangavelu, Pulari U and Gupta, Vipul and Dixit, Narendra M (2014) Estimating the fraction of progeny virions that must incorporate APOBEC3G for suppression of productive HIV-1 infection. In: VIROLOGY, 449 . pp. 224-228.

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Official URL: http://dx.doi.org/10.1016/j.virol.2013.11.026

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 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.

Item Type: Journal Article
Additional Information: Copyright for this article belongs to the ACADEMIC PRESS INC ELSEVIER SCIENCE, USA
Keywords: APOBEC; Vif; Hypermutation; Extinction threshold; Mathematical model; Stochastic simulations; Viral dynamics
Department/Centre: Division of Mechanical Sciences > Chemical Engineering
Depositing User: Id for Latest eprints
Date Deposited: 25 Feb 2014 08:35
Last Modified: 25 Feb 2014 08:35
URI: http://eprints.iisc.ac.in/id/eprint/48464

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