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Experimental evidence on Zika virus and birth defects in a mouse model

A paper published today in Nature (doi:10.1038/nature18296) has reported the first experimental evidence that the Zika virus can cause neurological defects in an animal model (in this case, a mouse).

In response, Professor Daniel Altmann, British Society for Immunology spokesperson and Professor of Immunology at Imperial College London, said:

“The current Zika virus outbreak has been especially alarming due to the association with a sharp spike in foetal microcephaly. This has been the key feature distinguishing the recent experience in Brazil from previous encounters with Zika in Africa or French Polynesia. However, evidence that Zika is truly causal in this microcephaly spike and, if so, how it happens, has been building incrementally over the past months. Earlier evidence has been of virus isolation from placenta and from blood and brain tissue of affected foetuses as well findings on infection of human neural stem cells.

“Now, Cugola, Fernandes, Russo and colleagues in Sao Paulo have looked at this by injecting pregnant female mice, about halfway through gestation, with a Brazilian variant of the virus. The litters, while not displaying the full features of microcephaly per se, show many signs of cortical malformation reminiscent of findings in human foetuses. This opens the door to mechanistic studies to understand the mode of its attack on nerve cells of this virus and molecular pathways of this mode of pathogenesis.    

“Meanwhile, the mouse studies leave many unknowns: Can this help to illuminate why, of Zika–exposed populations, increased cases of microcephaly are being reported largely from Brazil, and from some regions much more than others? What are the features of the viral sequences present in Brazil that account for differences in pathogenesis from the African sequences? And what lessons of variability in host susceptibility can be learnt from the fact that, in this study, one mouse strain was susceptible, the other absolutely resistant?” 


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