New TAU study identifies genes that can protect cells from Zika virus

Research may eventually lead to "a novel antiviral therapy" to fight the virus, which has affected over 60 million people worldwide, often causing severe brain anomalies in infants.

July 28, 2019 11:55
2 minute read.

A research scientist holds a vial marked "Zika" . (photo credit: REUTERS)

A new study by Tel Aviv University has used a genetic screen to identify genes that protect cells from the Zika [ZIKV] viral infection. The research, led by Dr. Ella H. Sklan of TAU's Sackler School of Medicine, was published in the Journal of Virology on May 29.

The study was based on a modification of the CRISPR-Cas9 gene-editing technique. CRISPR-Cas9 is a naturally occurring bacterial genome editing system that has been adapted to gene editing in the cells of mammals. The system is based on the bacterial enzyme Cas9, which can locate and modify specific locations along the human genome. A modification of this system, known as CRISPR (clustered regularly interspaced short palindromic repeats) activation, is accomplished by genetically changing Cas9.

"CRISPR activation can be used to identify genes protecting against viral infection," Sklan said. "We used this adapted system to activate every gene in the genome in cultured cells. We then infected the cells with the Zika virus. While most cells die following the infection, some survived due to the over-expression of some protective genes. We then used next-generation sequencing and bioinformatic analysis to identify a number of genes that enabled survival, focusing on one of these genes called IFI6. A previous screen conducted by another research group had identified this gene with respect to its role vis-à-vis other viruses.

"IFI6 showed high levels of protection against the Zika virus, both by protecting cells from infection and by preventing cell death," he continued. "If its yet unknown mode of action can be mimicked, it may one day serve as the basis for the development of a novel antiviral therapy to fight the Zika virus or related infections."

Together with Dr. Nabila Jabrane-Ferrat of The French National Center for Scientific Research, Sklan moved the study of the identified genes into Zika-infected human placenta tissues. These genes were induced following infection, indicating that they might play a protective role in this tissue as well.

"Our results provide a better understanding of key host factors that protect cells from ZIKV infection, and might assist in identifying novel antiviral targets," Sklan concluded.

The Zika virus has affected over 60 million people worldwide and can be passed on from a pregnant woman to her unborn fetus, leading to microcephaly [small head/brain] and other severe brain anomalies in the infant. There is currently no vaccine or specific treatment for the virus.

In early 2015, a widespread epidemic of Zika fever, originating in Brazil, spread to other parts of South and North America.

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