Using a molecular scalpel to understand virus-host interactions

CRISPR-Cas has been quite popular nowadays, unfortunately, due to controversies about experiments on human babies. However, we applied the CRISPR technology to determine genes that have an important function during Zika virus infection.

Dangerous mosquitos

Zika virus belongs to the family of Flaviviruses, a family of RNA viruses with a lot of mosquito-borne viruses, including Dengue virus, West Nile virus and Yellow Fever virus. You may have heard a lot about Zika in 2016 and 2017 as there was a major outbreak in the northern half of South America. For adults, the Zika virus disease itself generally has mild symptoms like fever, muscle and joint pain, and conjunctivitis. Most people do not develop any symptoms at all, and if they do, they typically last for only a week.

On the other hand, studies show an increased risk of neurologic complications associated with Zika virus infections including the Guillain-Barré syndrome. The most infamous association with Zika virus is that an infection during pregnancy can cause infants to be born with microcephaly and other congenital malformations. Other risks include preterm birth and miscarriage. Unfortunately, there is no vaccine or specific treatment, yet.

The secret of the surviving cells

With our CRISPR study, we aimed to identify host genes that protect and/or rescue host cells from Zika virus infection. Using a modified version of the CRISPR technology, specific genes were activated, which means that they were transcribed and translated into protein at a higher rate than usual. For each cell, a different gene was activated. After Zika infection, we analyzed the transcriptome of the surviving cells: which genes have been strongly activated? Those genes may be the ones rescuing the cell from Zika virus infection. Most of the identified genes have already been reported to have antiviral effects in other viruses as well. Apparently, interferon-stimulated genes have an effect at an early phase of viral infection and our study indicates that they interfere with the formation of the viral replication complex.

Using CRISPR technology to identify crucial host genes for different virus families is a promising tool to understand the virus-host interaction and design novel and specific therapies. We would like to thank our collaborators Anna Dukhovny and Ella Sklan from the Tel Aviv University for joining forces to conduct this exciting and important study.

[bibtex file= key=Dukhovny:19]

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