Experimental decoy molecules may be able to keep two types of deadly viruses from infecting human cells, researchers reported in two separate papers.
Their discovery of how these viruses enter cells, and the subsequent development of the decoys, potentially sets the stage for new strategies to prevent and treat tick-borne encephalitis viruses, which infect the central nervous system, and the yellow fever virus, which in severe cases can cause liver failure, bleeding, and shock, the researchers said.
"There are no treatments for these viral infections, so there is an urgent need for new strategies to prevent and treat these infections, which continue to cause severe disease and death in far too many cases," Dr. Michael Diamond of WashU Medicine in St. Louis, the senior author of both papers, said in a statement.
The researchers used genetic techniques, including CRISPR gene editing technology, to determine that the viruses use a family of proteins on human cell surfaces called low-density lipoprotein receptors (LDLR) as their main route of entry.
These proteins were already known to be entry routes for other types of viruses.
The yellow fever virus latches onto LDLRs called LRP1, LRP4 and VLDLR, the researchers reported in Nature.
Tick-borne encephalitis viruses enter cells via a different receptor, LRP8, they reported in PNAS.
Removing these receptor proteins from the surfaces of cells blocked the viruses from infecting those cells, the researchers said.
For both types of viruses, the researchers also designed "decoy" molecules. Carrying a small piece of the entry-receptor proteins, the decoys trick the viruses into latching on, thereby protecting cells from infection.
The decoy molecules prevented infection in human and mouse cells in test tubes. In mice, the decoys protected against a lethal dose of yellow fever virus and also prevented the liver damage typically caused by the virus.
"Our studies showing how these viruses get into cells creates opportunities to disrupt those routes, stopping viral infections from jumping animal species — both wild and domesticated — and spreading through populations of people," Diamond said.
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