Study reveals natural process that blocks viruses

April 17, 2013, University of Southern California

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. 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 , , , and SARS," said Jae U. Jung, principal investigator and distinguished professor and chair of the and Immunology Department. The study, "The antiviral effector IFITM3 disrupts intracellular cholesterol homeostasis to block viral entry," was published in the journal Cell Host & Microbe on April 17, 2013.

"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.

Joining Jung in the study were Samad Amini-Bavil-Olyaee, Keck School postdoctoral research associate and first author of the paper, as well as Youn Jung Choi, Keck School graduate student and second author, and researchers from the University of California, Riverside and Scripps Research Institute. The research was funded by the National Institutes of Health (grants CA082057, CA31363, CA115284, DE019085, AI073099, AI083025, HL110609) and the Fletcher Jones Foundation.

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.

Jung explained that in the most recent investigation, the rise in cholesterol was found to occur in the endosome compartment within the . "The membrane is usually very flexible," he said. "With an increase in cholesterol it becomes rigid, and doesn't allow viruses to pass through the endosome compartment into cytosol, the fluid portion inside cells. We were surprised to find that changing the balance of cholesterol concentration affects viral entry."

The next step, he said, "will be to identify a therapeutic molecule that activates the expression and function of the IFITM3 protein, which potentially can be used to create an anti-viral therapy. It could target the endosome compartment in order to control, combat, or prevent the spread of viral infection."

Explore further: Study reveals insight into how key protein protects against viral infections

Related Stories

Study reveals insight into how key protein protects against viral infections

April 2, 2012
Scientists from the University of Utah School of Medicine have discovered that a mouse protein called IFITM3 contributes to the body's defense against some types of viral infections by binding to an enzyme responsible for ...

Newly identified natural protein blocks HIV, other deadly viruses

February 11, 2013
A team of UCLA-led researchers has identified a protein with broad virus-fighting properties that potentially could be used as a weapon against deadly human pathogenic viruses such as HIV, Ebola, Rift Valley Fever, Nipah ...

New findings into conquering influenza

January 29, 2013
Reseachers from the University of Melbourne and The Walter and Eliza Hall Institute (WEHI) have discovered a new protein that protects against viral infections such as influenza.

Recommended for you

Magnetically applied MicroRNAs could one day help relieve constipation

January 17, 2018
Constipation is an underestimated and debilitating medical issue related to the opioid epidemic. As a growing concern, researchers look to new tools to help patients with this side effect of opioid use and aging.

Researchers devise decoy molecule to block pain where it starts

January 16, 2018
For anyone who has accidentally injured themselves, Dr. Zachary Campbell not only sympathizes, he's developing new ways to blunt pain.

Scientists unleash power of genetic data to identify disease risk

January 16, 2018
Massive banks of genetic information are being harnessed to shed new light on modifiable health risks that underlie common diseases.

Blood-vessel-on-a-chip provides insight into new anti-inflammatory drug candidate

January 15, 2018
One of the most important and fraught processes in the human body is inflammation. Inflammatory responses to injury or disease are crucial for recruiting the immune system to help the body heal, but inflammation can also ...

Molecule produced by fat cells reduces obesity and diabetes in mice

January 15, 2018
UC San Francisco researchers have discovered a new biological pathway in fat cells that could explain why some people with obesity are at high risk for metabolic diseases such as type 2 diabetes. The new findings—demonstrated ...

Obese fat becomes inflamed and scarred, which may make weight loss harder

January 12, 2018
The fat of obese people becomes distressed, scarred and inflamed, which can make weight loss more difficult, research at the University of Exeter has found.

2 comments

Adjust slider to filter visible comments by rank

Display comments: newest first

PhyOrgSux
1 / 5 (3) Apr 17, 2013
Someone did not use a spellchecker. "Stuyd reveals..." should of course be "Study reveals..."
Dug
1 / 5 (1) Apr 17, 2013
Don't most non-specific immune stimulants like the yeast derived beta 1-3 D glucan produce cytokine cascades - including interferon production? Unfortunately, that's a natural product and not a potential drug and consequently no pharmaceutical researcher will look at this.

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.