New gene editing study uncovers protective genes against Zika virus

Scientists in Tel Aviv have discovered some genes that protect the host organism from Zika virus attacks, giving hope for a vaccine or cure for this terrible viral disease.

Zika virus, which is prevalent in South America, can cause serious damage, including death or fetal birth, as well as serious conbad malformations, collectively known as conbad Zika syndrome. This includes problems such as a significant and disabling reduction in head size (microcephaly), neurological abnormalities, and delayed development. So far, more than 60 million people have been affected by this insect-borne virus, which can also be the cause of paralyzing disease of Guillain-Barré syndrome and others. nervous diseases. However, scientists have not developed a vaccine or treatment for this devastating disease.

An illustration of the Zika virus, whose symptoms include mild headaches, maculopapular rash, fever, malaise, conjunctivitis and arthralgia. – Illustration credit: AuntSpray / Shutterstock

The ongoing study at Tel Aviv University used a genome-wide genome screen, using a modified gene editing technique based on CRISPR-Cas9 technology. It is a platform derived from nature that plays a role in modifying the genome of bacteria under natural conditions. It has been adapted for use in mammalian cells under experimental conditions.

The system is built around the Cas9 bacterial enzyme that both locates specific gene locations along the DNA strands in humans and can alter them. By introducing a genetic modification in Cas9, the system is replaced by a variant called CRISPR activation. This helps the researchers to obtain gene expression in the same loci as those normally encountered in nature.

This modified CRISPR activation system is of great use when it comes to finding genes that can protect against viral infection. The process begins with the activation of all the genome genes of a cell in culture using their own promoters in the DNA strand. The cells are then allowed to be infected with the Zika virus. Most cells die from infection. In survivors, the reason is to look for high levels of expression of certain genes that therefore protect against infection.

The next step for researchers was to use next generation genome sequencing technology, combined with advanced bioinformatics, to reveal survival genes. These included certain genes called interferon-stimulated genes or ISGs, which are already known to protect the body against other viral infections. Subsequently, researchers discovered that two of these genes were most likely to be responsible for preventing infection. These are IFNL2 and IFI6.

When they are activated, these genes offer strong protection against viral infection at an early stage. Even when cells were infected in the presence of these genes, their cell death rate was lower than that of negative cells. These genes thus rescue the cells exposed to the Zika virus either from the infection itself or from the badociated cell death.

The present study focuses on one of the identified genes, namely IFI6. Senior researcher Ella Sklan says, "IFI6 has shown high levels of protection against Zika virus, both by protecting cells from infection and by preventing cell death."

Next, the team examined the placental tissue of Zika-infected mothers who had given birth. Indeed, the placenta is an entry point for the transmission of the virus from the mother to the fetus before birth. The researchers found a higher expression of these protective genes in infected placental tissues, suggesting a potential role in protecting the placenta from infection.

The importance of this discovery is to reveal some important factors that help prevent Zika virus infection of exposed cells. Sklan explains, "Our findings provide a better understanding of the key factors of the host that protect cells from infection at Zika and could help identify new antiviral targets."

However, no one yet knows how the gene works to do it. The search for the protection mechanism, which could allow scientists to develop new types of antiviral treatment against a whole family of viruses like Zika, is open. The CRISPR activation technology has also been proven in identifying host protection factors during infections.

The study was published in Virology Journal May 29, 2019.