Although the Zika virus tends to cause few, if any, symptoms in the adults it infects, its effects on embryos and fetuses can be devastating. Outbreaks in Brazil and Central America only in the past year have been tied to increases in congenital neurodevelopmental conditions, particularly microcephaly. Even more recently, studies have shown that Zika can infect human neural stem cells growing as brain organoids and can block neurogenesis in mice. But the mechanisms the virus uses to disrupt brain development are not understood.
At Tuesday’s microsymposium on cell division in development and disease, however, Andrew Kodani discussed his latest findings: That Zika disrupts centriole biogenesis in a manner similar to the autosomal recessive disorder that causes primary microcephaly, or MCPH.
Kodani, who recently moved from a postdoctoral fellowship at the University of California San Francisco to become a pediatric research fellow at Boston Children’s Hospital, said his study was quick follow-on work to findings he and his colleagues highlighted on the cover of the November issue of Neuron.
“Zika is the largest global pandemic of the past century,” he said. So when his earlier work revealed that alterations in the links between centrioles, apical proteins, and cell fate can dynamically regulate brain size, it made sense to ask whether Zika-caused microcephaly followed the same pathway.
In short, the answer appears to be “yes.” Perhaps even more importantly, Kodani and his team found a tantalizing clue about a possible therapeutic agent: An anthracene compound that’s been shown to stave off the effects of dengue, which is in the same virus family as Zika.
Kodani said that introducing as little as one micromolar of the compound ARDP0006 to his cell cultures blocked the accumulation of proteins that were preventing centrioles from duplicating.
“We can’t vouch for its efficacy,” he said. “All we know is that it works in cell culture.” He said that two of his former colleagues at UCSF, Joe DiRisi and Jeremy Reiter, are delving deeper into the compound’s therapeutic potential.