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Zika plasma viral dynamics in nonhuman primates provides insights into early infection and antiviral strategies.

Zika plasma viral dynamics in nonhuman primates provides insights into early infection and antiviral strategies.
Author Information (click to view)

Best K, Guedj J, Madelain V, de Lamballerie X, Lim SY, Osuna CE, Whitney JB, Perelson AS,


Best K, Guedj J, Madelain V, de Lamballerie X, Lim SY, Osuna CE, Whitney JB, Perelson AS, (click to view)

Best K, Guedj J, Madelain V, de Lamballerie X, Lim SY, Osuna CE, Whitney JB, Perelson AS,

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Proceedings of the National Academy of Sciences of the United States of America 2017 08 01114(33) 8847-8852 doi 10.1073/pnas.1704011114

Abstract

The recent outbreak of Zika virus (ZIKV) has been associated with fetal abnormalities and neurological complications, prompting global concern. Here we present a mathematical analysis of the within-host dynamics of plasma ZIKV burden in a nonhuman primate model, allowing for characterization of the growth and clearance of ZIKV within individual macaques. We estimate that the eclipse phase for ZIKV, the time between cell infection and viral production, is most likely short (∼4 h), the median within-host basic reproductive number R0 is 10.7, the rate of viral production is rapid (>25,000 virions d(-1)), and the lifetime of an infected cell while producing virus is ∼5 h. We also estimate that the minimum number of virions produced by an infected cell over its lifetime is ∼5,500. We assess the potential effect of an antiviral treatment that blocks viral replication, showing that the median time to undetectable plasma viral load (VL) can be reduced from ∼5 d to ∼3 d with a drug concentration ∼15 times the drug’s EC50 when treatment is given prophylactically starting at the time of infection. In the case of favipiravir, a polymerase inhibitor with activity against ZIKV, we predict a dose of 150 mg/kg given twice a day initiated at the time of infection can reduce the peak median VL by ∼3 logs and shorten the time to undetectable median VL by ∼2 d, whereas treatment given 2 d postinfection is mostly ineffective in accelerating plasma VL loss in macaques.

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