Zika disrupts cellular processes to impair brain development

VANCOUVER — Zika virus’s tricks for interfering with human brain cell development may also be the virus’s undoing.

Zika infection interferes with DNA replication and repair machinery and also prevents production of some proteins needed for proper brain growth, geneticist Feiran Zhang of Emory University in Atlanta reported October 19 at the annual meeting of the American Society of Human Genetics.

Levels of a protein called p53, which helps control cell growth and death, shot up by 80 percent in human brain cells infected with the Asian Zika virus strain responsible for the Zika epidemic in the Americas, Zhang said. The lab dish results are also reported in the Oct. 14 Nucleic Acids Research. Increased levels of the protein stop developing brain cells from growing and may cause the cells to commit suicide.
A drug that inactivates p53 stopped brain cells from dying, Zhang said. Such p53 inhibitors could help protect developing brains in babies infected with Zika. But researchers would need to be careful giving such drugs because too little p53 can lead to cancer.

Zika also makes small RNA molecules that interfere with production of proteins needed for DNA replication, cell growth and brain development, Zhang said. In particular, a small viral RNA called vsRNA-21 reduced the amount of microcephalin 1 protein made in human brain cells in lab dishes. The researchers confirmed the results in mouse experiments. That protein is needed for brain growth; not enough leads to the small heads seen in babies with microcephaly. Inhibitors of the viral RNAs might also be used in therapies, Zhang suggested.