Zika plasma viral dynamics in nonhuman primates provides insights into early infection and antiviral strategies.
Proc Natl Acad Sci U S A
; 114(33): 8847-8852, 2017 08 15.
Article
em En
| MEDLINE
| ID: mdl-28765371
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 (â¼4 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 â¼5 h. We also estimate that the minimum number of virions produced by an infected cell over its lifetime is â¼5,500. 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 â¼5 d to â¼3 d with a drug concentration â¼15 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 â¼3 logs and shorten the time to undetectable median VL by â¼2 d, whereas treatment given 2 d postinfection is mostly ineffective in accelerating plasma VL loss in macaques.
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Base de dados:
MEDLINE
Assunto principal:
Antivirais
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Replicação Viral
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Carga Viral
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Zika virus
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Infecção por Zika virus
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Modelos Biológicos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Ano de publicação:
2017
Tipo de documento:
Article