A coalition of Ohio and California-based researchers have unveiled in a first of its kind study how infection of the Zika virus results in birth defects among pregnant women.
As described in Nature Microbiology, the most common outcome of the Zika virus infection is brain calcification, which is linked to defects in infancy, affecting cognition and causing motor disorders, eye abnormalities, hearing deficits, and seizures.
“In perivascular cells, bone morphogenetic protein (BMP) is an osteogenic factor that undergoes maturation to activate osteogenesis and calcification,” according to researchers.
“We show that ZIKV infection of cultivated primary human brain pericytes triggers BMP2 maturation, leading to osteogenic gene expression and calcification. We observed extensive calcification near ZIKV+ pericytes of fetal human brain specimens and in vertically transmitted ZIKV+ human signal transducer and activator of transcription 2-knockin mouse pup brains,” researchers also stated in their article.
The study uncovered that once fetal-derived pericytes were infected with the virus, the BMP2 gene, along with numerous downstream osteogenic genes, were expressed at higher levels, leading to brain calcification. THe BMP-related genes functioned distinctly when under infection with Zika, in comparison with its function during normal development.
“Not only did ZIKV NS3 expression alone induce BMP2 maturation, osteogenic gene expression and calcification, but purified NS3 protease also effectively cleaved pro-BMP2 in vitro to generate biologically active mature BMP2,” said Weiqiang Chen, and fellow colleagues, in the findings.
“These findings highlight ZIKV-induced calcification where the NS3 protease subverts the BMP2-mediated osteogenic signalling pathway to trigger brain calcification.”