American Strain of Zika Virus Causes More Severe Microcephaly Than an Old Asian Strain in Neonatal Mice

Zika virus (ZIKV) has evolved from an overlooked mosquito-borne flavivirus into a global health threat due to its astonishing causal link to microcephaly and other disorders. ZIKV has been shown to infect neuronal progenitor cells of the fetal mouse brain, which is comparable to the first-trimester human fetal brain, and result in microcephaly. However, whether there are different effects between the contemporary ZIKV strain and its ancestral strain in the neonatal mouse brain, which is comparable with the second-trimester human fetal brain, is unclear. Here we adopted a mouse model which enables us to study the postnatal effect of ZIKV infection. We show that even 100 pfu of ZIKV can replicate and infect neurons and oligodendrocytes in most parts of the brain. Compared with the ancestral strain from Cambodia (CAM/2010), infection of the ZIKV strain from Venezuela (VEN/2016) leads to much more severe microcephaly, accompanied by more neuronal cell death, abolishment of oligodendrocyte development, and a more dramatic immune response. The serious brain damage caused by VEN/2016 infection would be helpful to elucidate why the American strain resulted in severe neurovirulence in infants and will provide clinical guidance for the diagnosis and treatment of infection by different ZIKV strains.
Highlights • The infection of an American strain of ZIKV leads to more severe microcephaly than the ancestral Asian strain. • American strain infects more cells, and induces more dramatic immune response and cell death than ancestral Asian strain. World attention has been drawn to a global Zika virus (ZIKV) outbreak due to its unexpected causal link to congenital brain abnormalities, especially microcephaly. Infection of pregnant women with the American Zika strain, but not the ancestral Asian strain, can result in microcephaly in infants. However, the phenotypic difference between the contemporary American strain and ancestral Asian strain of ZIKV is still unclear. We employed the ZIKV infection model of a neonatal mouse brain to compare the difference between these two strains. We find that infection by the American strain leads to more severe microcephaly than the ancestral Asian strain.