Navigation Links
Team learns how cellular protein detects viruses and sparks immune response

A study led by researchers at the University of Illinois reveals how a cellular protein recognizes an invading virus and alerts the body to the infection.

The research, described this week in the journal Science and led by Illinois physics professor and Howard Hughes Medical Institute investigator Taekjip Ha, settles a debate over how the protein, RIG-I (pronounced rig-EYE), is able to distinguish between viral RNA and self (or cellular) RNA.

"RIG-I is the first molecule in the immune response to detect viral RNA," said Sua Myong, lead author on the study and a professor at the U. of I.'s Institute for Genomic Biology. Unlike most other proteins known to detect viral infections only in specialized immune cells, RIG-I is active in every cell type in the body, she said.

The RIG-I protein has two major parts: caspase-recruitment domains (CARDs) and an ATPase domain that consumes ATP, the cellular fuel molecule.

Previous studies had shown that the CARD domains actually inhibit the activity of RIG-I when no virus is present, but are vital to sounding the alarm and triggering an immune response once a certain type of virus has been detected.

Other studies had found that RIG-I recognizes an important feature of viral RNAs that is missing from most human RNAs. This feature, a "triphosphate" tag at a particular end, the "five-prime" (5') end, of viral RNA, is a viral fingerprint that tells RIG-I that something is amiss. Detection of this tag starts a cascade of reactions that allows RIG-I to broadcast a message to other cellular components, and ultimately to other cells.

The researchers also knew that RIG-I was usually active in the presence of double-stranded RNA, not the single-stranded RNA found in most animal cells.

Earlier research had also shown that the central ATPase domain is critical to the function of the molecule. A single mutation in this region shuts down its activity altogether.

"We knew that the CARD domain was responsible for transmitting the antiviral signaling," Myong said. "And we knew how the 5'-triphosphate tag is detected. But a big question remained about the ATPase domain: It was using ATP to do something but what?"

To solve that mystery, the researchers used a technique termed "protein-induced fluorescent enhancement." This method makes use of a fluorescent dye that, when attached to a specific region of a molecule such as RNA, glows with more or less intensity depending on its proximity to a protein that is interacting with that molecule.

Using this technique, the researchers found that the RIG-I protein moves back and forth (translocates) selectively on double-stranded RNA, and that this activity is greatly stimulated in the presence of 5'-triphosphate.

By requiring both the 5'-triphosphate and the double-stranded RNA for it to function, the RIG-I protein is able to very accurately detect a viral invader, said Ha.

Most cellular RNAs have their triphosphate tails bobbed, capped or otherwise modified before circulating in the cytosol of the cell, he said. "So this is one powerful way of distinguishing viral RNA from cellular RNA."

Prior to this study, researchers did not know if RIG-I sensed both the double-stranded RNA and the 5'-triphosphate separately, or in an integrated manner, said Myong.

"Our work bridges the gap," she said. "We show that it does both in an integrated manner."


Contact: Diana Yates
University of Illinois at Urbana-Champaign

Related medicine news :

1. LearnSomething Names Deborah Faucette to New Position of Senior Vice President of Sales and Marketing
2. Congressman Hoekstra Tours Holland Pathology Laboratory; Learns Vital Role In Patient Care
3. Congressman Altmire Tours Womens Health Clinical Laboratory; Learns Vital Role in Patient Care
4. Congressman Buchanan Tours Florida Clinical Laboratory; Learns Vital Role in Patient Care
5. To bet or not to bet: How the brain learns to estimate risk
6. Researchers develop neural implant that learns with the brain
7. Pharmavite Partners With LearnSomething, Inc. on Consumer Education Program, LearnSomethingAbout(TM)
8. Story ideas from molecular & cellular proteomics
9. A Chinese medicine compound has satisfactory anti-cancer effects on hepatocellular carcinoma
10. ReCellular Named Exclusive Cell Phone Recycling Partner for Consumer Cellular
11. Intra-arterial combination chemotherapy induces long-term survival for hepatocellular carcinoma
Post Your Comments:
Related Image:
Team learns how cellular protein detects viruses and sparks immune response
(Date:6/26/2016)... Michigan (PRWEB) , ... June 26, 2016 , ... ... to fertility once they have been diagnosed with endometriosis. These women need a ... they also require a comprehensive approach that can help for preservation of fertility ...
(Date:6/25/2016)... ... ... closing of Bruton Memorial Library on June 21 due to a possible lice infestation, as ... of head lice: the parasite’s ability to live away from a human host, and to ... one in the event that lice have simply gotten out of control. , As lice ...
(Date:6/25/2016)... CA (PRWEB) , ... June 25, 2016 , ... As ... with Magna Cum Laude and his M.D from the David Geffen School of Medicine ... and returned to Los Angeles to complete his fellowship in hematology/oncology at the UCLA-Olive ...
(Date:6/25/2016)... ... June 25, 2016 , ... Conventional wisdom preaches the benefits of moderation, ... the latter, setting the bar too high can result in disappointment, perhaps even self-loathing. ... toward their goal. , Research from reveals that behind the ...
(Date:6/24/2016)... ... June 24, 2016 , ... June 19, 2016 is World Sickle ... chronic pain and the benefits of holistic treatments, Serenity Recovery Center of ... Sickle Cell Disease. , Sickle Cell Disease (SCD) is a disorder of the red ...
Breaking Medicine News(10 mins):
(Date:6/24/2016)... , June 24, 2016  Arkis BioSciences, a ... invasive and more durable cerebrospinal fluid treatments, today ... The Series-A funding is led by Innova Memphis, ... and other private investors.  Arkis, new financing will ... and the market release of its in-licensed Endexo® ...
(Date:6/23/2016)... a startling report released today, National Safety Council research ... proven plan to eliminate prescription opioid overdoses. Prescription Nation ... tackling the worst drug crisis in recorded U.S. history, assigned a ... , New Mexico , Tennessee ... failing states, three – Michigan , ...
(Date:6/23/2016)... 23, 2016 Bracket , a leading clinical ... generation clinical outcomes platform, Bracket eCOA (SM) 6.0, at ... 26 – 30, 2016 in Philadelphia , ... Outcome Assessment product of its kind to fully integrate with ... Bracket eCOA 6.0 is a flexible platform for electronic clinical ...
Breaking Medicine Technology: