Potential drug target identified for Zika, similar viruses

June 17, 2016

Scientists potentially have found a way to disrupt Zika and similar viruses from spreading in the body.

A team at Washington University School of Medicine in St. Louis has identified a single gene pathway that is vital for Zika and other flaviviruses to spread infection between cells. Further, they showed that shutting down a single gene in this pathway -- in both human and insect cells -- does not negatively affect the cells themselves and renders flaviviruses unable to leave the infected cell, curbing the spread of infection.

The study, published June 17 in Nature, points to a potential drug target for Zika and other flaviviruses such as dengue and West Nile that have major impacts on public health.

"We wanted to find out if we could identify genes present in the host cells that are absolutely required by the virus for infection," said senior author Michael Diamond, MD, PhD, the Herbert S. Gasser Professor of Medicine. "Out of about 19,000 genes that we looked at, we only found nine key genes that the virus relies on for infection or to spread. All of them are associated with an important part of the cell that processes viral particles, which is essential to spreading the infection."

To identify genes that flaviviruses rely on, Diamond and his colleagues utilized a gene editing technology called CRISPR that is capable of selectively shutting down individual genes. Viruses must hijack host cells to replicate and spread, making them dependent upon the genetic material of the organisms they infect. If a cell lacks a gene that the virus requires for infection, the virus will be stopped in its tracks, and the cell will survive. Such evidence indicates that the missing gene is vital to viral spread and should be studied further.

Of the nine key genes Diamond and his colleagues identified, one called SPCS1, when disabled, not only reduces viral infection but appears to have no adverse effects on the cells the scientists studied. The researchers performed the first experiments on West Nile virus and then showed that the same results held true for other Flaviviridae family members, including Zika, dengue, yellow fever, Japanese encephalitis and hepatitis C viruses.

While the absence of this gene shut down the spread of flaviviruses, the researchers found that eliminating the gene had no detrimental effect on other types of viruses, including alphaviruses, bunyaviruses and rhabdoviruses.

"Flaviviruses appear to be uniquely dependent on this particular gene to release the viral particle," Diamond said. "In these viruses, this gene sets off a domino effect that is required to assemble and release the viral particle. Without it, the chain reaction doesn't happen and the virus can't spread. So we are interested in this gene as a potential drug target because it disrupts the virus and does not disrupt the host."
-end-
This work was supported by the National Institutes of Health (NIH), grant numbers U19 AI083019, R01 AI104972, T32 AI007163, UL TR000448 and P41 GM103422-35; and the intramural program of the National Institute of Allergy and Infectious Disease.

Zhang R, Miner JJ, Gorman MJ, Rausch K, Ramage H, White JP, Zuiani A, Zhang P, Fernandez E, Zhang Q, Dowd KA, Pierson TC, Cherry S, Diamond MS. A CRISPR screen defines a signal peptide processing pathway required by flaviviruses. Nature. June 17, 2016.

Washington University School of Medicine's 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient-care institutions in the nation, currently ranked sixth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.

Washington University School of Medicine

Related West Nile Virus Articles from Brightsurf:

Rising temperatures could shift US West Nile virus transmission
West Nile virus spreads most efficiently in the US at temperatures between 24-25 degrees Celsius (75.2-77 degrees Fahrenheit), a new study published today in eLife shows.

West Nile virus triggers brain inflammation by inhibiting protein degradation
West Nile virus (WNV) inhibits autophagy -- an essential system that digests or removes cellular constituents such as proteins -- to induce the aggregation of proteins in infected cells, triggering cell death and brain inflammation (encephalitis), according to Hokkaido University researchers.

WSU study shows insulin can increase mosquitoes' immunity to West Nile virus
A discovery by a Washington State University-led research team has the potential to inhibit the spread of West Nile virus as well as Zika and dengue viruses.

Critical protein that could unlock West Nile/Zika virus treatments identified
A team of Georgia State scientists has identified a protein that is critical in controlling replication of West Nile and Zika viruses -- and could be important for developing therapies to prevent and treat those viruses.

West Nile virus in the New World: Reflections on 20 years in pursuit of an elusive foe
Though eradication of West Nile virus remains beyond our capability, the body of knowledge built since its arrival in the Americas in 1999 is now powering efforts to minimize its impact and prepare for the invasion of other mosquito-borne diseases.

Light pollution may be increasing West Nile virus spillover from wild birds
House sparrows infected with West Nile virus (WNV) that live in light polluted conditions remain infectious for two days longer than those who do not, increasing the potential for a WNV outbreak by about 41%.

Mount Sinai researchers find significant delays in West Nile virus reporting
Mount Sinai researchers found significant delays in reporting human cases of West Nile virus, hampering real-time forecasting of the potentially deadly mosquito-borne disease, according to a study in the JAMA Network Open in April.

Insecticide resistance genes affect vector competence for West Nile virus
In a context of overuse of insecticides, which leads to the selection of resistant mosquitoes, it is already known that this resistance to insecticides affects interactions between mosquitoes and the pathogens they transmit.

Where will the world's next Zika, West Nile or Dengue virus come from?
Scientists from the University of California, Davis, have identified wildlife species that are the most likely to host flaviviruses such as Zika, West Nile, dengue and yellow fever.

Vanderbilt discovery could neutralize West Nile virus
Researchers at Vanderbilt University Medical Center and colleagues have isolated a human monoclonal antibody that can 'neutralize' the West Nile virus and potentially prevent a leading cause of viral encephalitis (brain inflammation) in the United States.

Read More: West Nile Virus News and West Nile Virus Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.