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Proc Natl Acad Sci U S A. 2017 Aug 15;114(33):8847-8852. doi: 10.1073/pnas.1704011114. Epub 2017 Aug 1.

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

Author information

1
Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM 87545.
2
Infection, Antimicrobials, Modelling, Evolution, UMR 1137, INSERM, Université Paris Diderot, Sorbonne Paris Cité, F-75018 Paris, France.
3
UMR Emergence des Pathologies Virales, Aix-Marseille University, Institut de Recherche pour le Développement 190, INSERM 1207, École des Hautes Études en Santé Publique, F-13385 Marseille, France.
4
UMR "Emergence des Pathologies Virales," Institut Hospitalo-Universitaire Méditerranée Infection, F-13385 Marseille, France.
5
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215.
6
Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139.
7
Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM 87545; asp@lanl.gov.

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.

KEYWORDS:

Zika virus; antiviral therapy; mathematical modeling; viral dynamics

PMID:
28765371
PMCID:
PMC5565429
DOI:
10.1073/pnas.1704011114
[Indexed for MEDLINE]
Free PMC Article

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