The genus of viruses known as the flaviviruses are emerging globally as a significant cause of human disease. A flavivirus currently in the news and causing a lot of concern is Zika virus. Other medically important flaviviruses include dengue, yellow fever, St. Louis encephalitis, tick-borne encephalitis (TBE), Japanese encephalitis and West Nile viruses.
Flaviviruses contain a single-strand of RNA and can be transmitted to humans via a bite from an infected mosquito or tick. Human-to-human transmission of these viruses can also occur through transfusion of infected blood products or infected tissues.
Around the globe, hundreds of millions of people are infected every year by flaviviruses but no antiviral therapies are available. Currently there are vaccines against yellow fever, TBE and Japanese encephalitis, with further vaccines being developed. Disease control is heavily reliant on vector (mosquito and tick) control and vaccine development and use.
Since viruses are reliant upon the hosts cellular machinery to replicate and infect other cells, it is possible to prevent further infection by disabling a component of the hosts cellular machinery that the virus needs. However, this is not always successful as the host cell may also be reliant upon the disabled component to survive.
A team of researchers from the Washington University School of Medicine (WUSM) have undertaken a genome-wide CRISPR/Cas9-based screen to identify host genes which are essential for flaviviral infection. Using the CRISPR/Cas9 gene editing technique, they were able to selectively edit the DNA of host genes until they discovered a gene, which when edited, resulted in reduced flavivirus infection.
In all, the team found nine human genes which are essential for flavivirus infectivity. These genes were associated with endoplasmic reticulum functions including translocation, protein degradation and N-linked glycosylation. In particular, a subset of endoplasmic reticulum-associated signal peptidase complex (SPCS) proteins are essential for flavivirus infectivity. The scientists were able to show that disabling these genes reduced flaviviral infection but had no detrimental effect on the host cells.
These genes are therefore potential targets for drug development to prevent flaviviral infections. This news is exciting given the current emergence and rapid spread of the Zika virus. Drug therapies to combat the spread of Zika virus will not be developed in time for the 2016 Olympics in Brazil but this research means there is hope for the future.