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

Authors:
; ; ; ; ; ; ;
Publication Date:
Sponsoring Org.:
USDOE
OSTI Identifier:
1373602
Grant/Contract Number:
AC52-06NA25396
Resource Type:
Journal Article: Published Article
Journal Name:
Proceedings of the National Academy of Sciences of the United States of America
Additional Journal Information:
Journal Volume: 114; Journal Issue: 33; Related Information: CHORUS Timestamp: 2017-11-14 14:01:41; Journal ID: ISSN 0027-8424
Publisher:
Proceedings of the National Academy of Sciences
Country of Publication:
United States
Language:
English

Citation Formats

Best, Katharine, Guedj, Jeremie, Madelain, Vincent, de Lamballerie, Xavier, Lim, So-Yon, Osuna, Christa E., Whitney, James B., and Perelson, Alan S. Zika plasma viral dynamics in nonhuman primates provides insights into early infection and antiviral strategies. United States: N. p., 2017. Web. doi:10.1073/pnas.1704011114.
Best, Katharine, Guedj, Jeremie, Madelain, Vincent, de Lamballerie, Xavier, Lim, So-Yon, Osuna, Christa E., Whitney, James B., & Perelson, Alan S. Zika plasma viral dynamics in nonhuman primates provides insights into early infection and antiviral strategies. United States. doi:10.1073/pnas.1704011114.
Best, Katharine, Guedj, Jeremie, Madelain, Vincent, de Lamballerie, Xavier, Lim, So-Yon, Osuna, Christa E., Whitney, James B., and Perelson, Alan S. Tue . "Zika plasma viral dynamics in nonhuman primates provides insights into early infection and antiviral strategies". United States. doi:10.1073/pnas.1704011114.
@article{osti_1373602,
title = {Zika plasma viral dynamics in nonhuman primates provides insights into early infection and antiviral strategies},
author = {Best, Katharine and Guedj, Jeremie and Madelain, Vincent and de Lamballerie, Xavier and Lim, So-Yon and Osuna, Christa E. and Whitney, James B. and Perelson, Alan S.},
abstractNote = {},
doi = {10.1073/pnas.1704011114},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
number = 33,
volume = 114,
place = {United States},
year = {Tue Aug 01 00:00:00 EDT 2017},
month = {Tue Aug 01 00:00:00 EDT 2017}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record at 10.1073/pnas.1704011114

Citation Metrics:
Cited by: 5works
Citation information provided by
Web of Science

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  • The recent outbreak of Zika virus (ZIKV) has been associated with fetal abnormalities and neurological complications, prompting global concern. Here we present the first mathematical analysis of the within-host dynamics of plasma ZiKV burden in a non-human primate model, allowing for characterization of the growth and clearance of ZIKV within an individual macaque.
  • Infection with Zika virus has been associated with serious neurological complications and fetal abnormalities. However, the dynamics of viral infection, replication and shedding are poorly understood. Here we show that both rhesus and cynomolgus macaques are highly susceptible to infection by lineages of Zika virus that are closely related to, or are currently circulating in, the Americas. After subcutaneous viral inoculation, viral RNA was detected in blood plasma as early as 1 d after infection. Viral RNA was also detected in saliva, urine, cerebrospinal fluid (CSF) and semen, but transiently in vaginal secretions. Although viral RNA during primary infection wasmore » cleared from blood plasma and urine within 10 d, viral RNA was detectable in saliva and seminal fluids until the end of the study, 3 weeks after the resolution of viremia in the blood. The control of primary Zika virus infection in the blood was correlated with rapid innate and adaptive immune responses. We also identified Zika RNA in tissues, including the brain and male and female reproductive tissues, during early and late stages of infection. Re-infection of six animals 45 d after primary infection with a heterologous strain resulted in complete protection, which suggests that primary Zika virus infection elicits protective immunity. Finally, early invasion of Zika virus into the nervous system of healthy animals and the extent and duration of shedding in saliva and semen underscore possible concern for additional neurologic complications and nonarthropod-mediated transmission in humans.« less
  • Thirteen female Rhesus macaques were intramuscularly injected with 90Sr(NO 3) 2 diluted in sodium citrate solution. The biokinetic data from these animals were compared against the predictions of the NCRP 156 wound models combined with the ICRP systemic models. We observed observed that the activities measured in plasma of these nonhuman primates (NHPs) were consistently lower than those predicted by the default human biokinetic models. The urinary excretion from the NHPs at times immediately after injection was much greater than that in humans. The fecal excretion rates were found to be in relatively better agreement with humans. Similarly, the activitiesmore » retained in the skeleton of the NHPs were lower than that in humans. These differences were attributed to the higher calcium diet of the NHPs (0.03 to 0.12 g/d/kg body weight) compared to that of humans. These observations were consistent with the early animal and human studies that showed the effect of calcium on strontium metabolism, specifically urinary excretion. Strontium is preferentially filtered at a much higher rate in kidneys than calcium because it is less completely bound to protein than is calcium. Furthermore, these differences, along with large inter-animal variability, should be considered when estimating the behavior of Sr in humans from the metabolic data in animals or vice-versa.« less
  • Here, the recent availability of extremely intense, femtosecond X-ray free-electron laser (XFEL) sources has spurred the development of serial femtosecond nanocrystallography (SFX). Here, SFX is used to analyze nanoscale crystals of β-hematin, the synthetic form of hemozoin which is a waste by-product of the malaria parasite. This analysis reveals significant differences in β-hematin data collected during SFX and synchrotron crystallography experiments. To interpret these differences two possibilities are considered: structural differences between the nanocrystal and larger crystalline forms of β-hematin, and radiation damage. Simulation studies show that structural inhomogeneity appears at present to provide a better fit to the experimentalmore » data. If confirmed, these observations will have implications for designing compounds that inhibit hemozoin formation and suggest that, for some systems at least, additional information may be gained by comparing structures obtained from nanocrystals and macroscopic crystals of the same molecule.« less