Postnatal Zika virus infection is associated with persistent abnormalities in brain structure, function, and behavior in infant macaques

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Science Translational Medicine  04 Apr 2018:
Vol. 10, Issue 435, eaao6975
DOI: 10.1126/scitranslmed.aao6975

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  • In response to Wei Liang
    • Maud Mavigner
    • Other Contributors:
      • Jessica Raper
      • Mar Sanchez
      • Ann Chahroudi

    The eLetter by Wei Laing raises the concern of natural variation in monkeys potentially influencing our results, specifically with regard to the lateral ventricle volume. The limitations of our study are detailed in the article and, in particular, we highlight the small sample size that allowed us to generate hypotheses (rather than definitive conclusions) regarding postnatal ZIKV infection in infant macaques. While variation naturally occurs in rhesus macaques, our inclusion of similarly-reared control infants treated with the same experimental conditions as a comparison to ZIKV-infected infants reduces the likelihood of inter-animal variation being the differentiating factor in this work. Furthermore, we reference the standard deviation in lateral ventricle volumes measured in prior work with colony-reared infant macaques that was less than the difference we observed between ZIKV-infected animals and controls. During this period of rapid brain development, the longitudinal assessment performed at 3 and 6 months in the same animals also allowed for the impact of natural variability at a single time point to be minimized. We take issue with the title of the eLetter (“RE: An imperfect design”) and suggest to Dr. Liang that novel nonhuman primate experiments are not meant to be “perfect”, but rather serve as a clinically-relevant translational model to generate hypotheses and bridge the gap between basic science and human trials.

    Competing Interests: None declared.
  • RE: An imperfect design

    This study mainly discusses the impact of Zika virus(ZIKV) on brain anatomy, histopathology and function of infant rhesus macaques(RMs). The article emphasize the difference between the experimental group and the control group in the volume of the lateral ventricle. However, Are these differences caused by viruses or natural variations of monkeys? It’s unknown now.As the study only acquired the MRI images at 3 months and 6 months after ZIKV infection, and did not have the MRI images before infection.Moreover, the sample size was small, so the effect of natural variation could not be ruled out. The results could be more persuasive if MRI images of all infant RMs could be obtained before infection. In general, the experiment is very meaningful.

    Competing Interests: None declared.