Zika virus has taken the world by storm in the last year--a virus that’s transmitted by a mosquito and can cause severe developmental malformations in the infected newly born. Researchers from the University of Southern California (USC) have recently identified key proteins involved in this disease, hinting at potential therapy to correct Zika-related malformations.
The results were published by senior author Jae Jung and his team in Cell Stem Cell.
The results of the study found that of the 10 proteins that make up the Zika virus, two proteins (NS4A and NS4B) are the key players in the development of abnormally small brains in infected babies, also known as microcephaly.
The scientists arrived at this major finding by studying three strains of Zika in the second trimester of human fetal neural stem cells.
"We now know the molecular pathway, so we made the first big step toward target therapy for Zika-induced microcephaly," Jung said. "Years from now, one shot or a series of shots could target the proteins NS4A and NS4B or their collaborators."
In the first known study to unveil Zika on a molecular level, the researchers find that the microcephaly-causing proteins interfere with the Akt-mTOR pathway. This pathway is recognized to be responsible for a normal biological function that recycles pathogens, however this process, known as autophagy, can also help viruses such as dengue, hepatitis C and Zika to proliferate.
"Zika loves and needs autophagy," Jung explains. "Zika raises the activity in this recycling factory so they can use the energy and nutrients there to replicate. It's possible that since Zika is using most of the energy, the neuronal stem cells are left with metabolic deficits. Thus the chances for them to differentiate and mature into neurons and other brain cell types is much lower."
Despite not every pregnant woman giving birth to a baby with microcephaly, the researchers emphasize that treatment would benefit a huge number of newly born infants. Jung and colleagues will further test the function of NS4A and NS4B proteins in mouse models, and in brain organoids derived from humans.
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