Zika virus (
ZIKV)
infection during
pregnancy can cause a set of severe
abnormalities in the
fetus known as
congenital Zika syndrome (CZS). Experiments with
animal models and
in vitro systems have substantially contributed to our
understanding of the pathophysiology of
ZIKV infection. Here, to investigate the molecular basis of CZS in
humans, we used a
systems biology approach to integrate transcriptomic, proteomic, and genomic data from the postmortem brains of
neonates with CZS. We observed that collagens were greatly reduced in expression in CZS brains at both the
RNA and
protein levels and that
neonates with CZS had several single-
nucleotide polymorphisms in
collagen-encoding
genes that are associated with
osteogenesis imperfecta and
arthrogryposis. These findings were validated by
immunohistochemistry and comparative
analysis of
collagen abundance in
ZIKV-infected and uninfected samples. In addition, we showed a
ZIKV-dependent increase in the expression of
cell adhesion factors that are essential for
neurite outgrowth and
axon guidance, findings that are consistent with the neuronal migration defects observed in CZS. Together, these findings provide insights into the underlying molecular alterations in the
ZIKV-infected
brain and reveal host
genes associated with CZS susceptibility.