Zika virus is an arthropod borne emerging pathogen cells causing febrile illness. This virus effecting over 60 million people, mostly in South America. It has potentially devastating consequences for pregnant women and their unborn children, many of whom are born with severe microcephaly and other developmental and neurological abnormalities. As there is currently no vaccine or specific treatment for the virus.
The study using a genetic screen to identify genes that protect cells from Zika viral infection. It may one day lead to the development of a treatment for the Zika virus and other infections. Basing on the 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 mammalian cells. As the system is basing on the bacterial enzyme Cas9; which can be locating and modifying specific locations along the human genome.
Genes that protecting cells
A modification of this system, known as CRISPR activation; is accomplishing by genetically changing in a way that enabling the expression of specific genes in their original DNA locations. CRISPR activation can be using to identify genes protecting against viral infection. The study using this adapting 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. On other hand the study using next-generation sequencing and bioinformatic analysis to identify a number of genes that enabled survival, focusing on one of these genes called IFI6. As IFI6 showing high levels of protection against the Zika virus both by protecting cells from infection and by preventing cell death.
But 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 relating infections; and identifying genes into Zika-infecting human placenta tissues, which serve as a gateway for viral transmission to the fetus. These genes were inducing following infection, indicating they might play a protective role in this tissue as well.
However, activation of these genes had an effect on an early stage in viral infection. In addition, infected cells expressing sgRNAs for both of these genes displayed lower levels of cell death compared to controls. Furthermore, the identifying genes were significantly inducing in ZIKV infecting placenta explants. Thus, these results highlight a set of ISGs directly relevant for rescuing cells from ZIKV infection or its associated cell death and substantiates CRISPR activation screens as a tool to identify host factors impeding pathogen infection.