Scientists at UMass Medical School have performed the first CRISPR/Cas9 screen to discover human proteins that Zika virus needs for replication. This work, led by Abraham Brass, MD, PhD, assistant professor in microbiology & physiological systems, reveals new leads that may be useful for halting Zika, dengue and other emerging viral infections. “These genetic screens give us our first look at what these viruses need to survive,” said Dr. Brass.
Using the RNAi and CRISPR/Cas9 screening technologies they’d developed for dengue and influenza, George Savidis, research associate, Paul Meraner, MD, postdoctoral fellow, and William M. McDougall, PhD, postdoctoral associate, in the Brass lab, began by knocking out or depleting each protein in the human genome one at a time, then seeing how Zika or dengue virus grew when that human protein was gone. Brass and colleagues identified multiple host proteins critical to both Zika and dengue viral replication. Among these was the AXL protein, which the virus uses to gain access to and enter the cell. They also identified the endoplasmic reticulum membrane protein complex (EMC) as critical to early-stage infection by the viruses. Together, these findings represent potential therapeutic targets that could help to treat and prevent infection. The next step is to develop therapies that inhibit Zika and dengue by targeting these proteins.
The study appears online in the journal Cell Reports.