The human body has the ability to ward off viruses by activating a naturally occurring protein at the cellular level, setting off a chain reaction that disrupts the levels of cholesterol required in cell membranes to enable viruses to enter cells, a new study has found.
The findings, discovered by researchers in molecular microbiology and immunology at the Keck School of Medicine of USC, hold promise for the development of therapies to fight a variety of viral infections.
“Previous studies have shown that our bodies are already equipped to block viruses such as Ebola, influenza, West Nile, and SARS,” Jae U. Jung, principal investigator and distinguished professor and chair of the Molecular Microbiology and Immunology Department, said.
“We showed how this occurs,” Jung said. “When a virus tries to enter, the immune system gets stimulated by interferon, which produces almost 300 host proteins, including IFITM3. This protein then disrupts the interaction between two other proteins, which, in turn, significantly increases the level of cholesterol in cells, and thereby blocks the virus.”
Jung added that the increase in cholesterol is only within the endosome compartment of cells and has no impact on or effect from the level of cholesterol in the bloodstream.
Scientists long have known that interferon, a protein released by the body`s cells and named after its ability to “interfere” with viral replication, can inhibit the spread of viruses, but didn`t understand how.
The Keck School investigators found that interferon-inducible transmembrane protein 3 (IFITM3) can disrupt the interaction between Vesicle-membrane-associated protein (VAPA) and oxysterol-binding protein (OSBP) that regulates the transport and stability of cholesterol, which are required for many viruses to take hold.
One of the main goals of his lab, Jung said, is to understand how the immune system recognizes viruses and blocks entry.
In previous research, he and his colleagues have shown that a specific immune protein recognizes genetic information of the virus and then sets off an alarm signal in the host immune system.
The study is published in the journal Cell Host and Microbe.