Featured Research

from universities, journals, and other organizations

Foot soldiers of the immune system

Date:
January 13, 2013
Source:
McGill University
Summary:
Researchers have discovered the molecular blueprint behind the IFIT protein. This key protein enables the human immune system to detect viruses and prevent infection by acting as foot soldiers guarding the body against infection. The findings are a promising step towards developing new drugs for combating a wide range of immune system disorders.

Researchers at McGill University and the Research Center for Molecular Medicine (CeMM) of the Austrian Academy of Sciences have discovered the molecular blueprint behind the IFIT protein. This key protein enables the human immune system to detect viruses and prevent infection by acting as foot soldiers guarding the body against infection. They recognize foreign viral ribonucleic acid (RNA) produced by the virus and act as defender molecules by potentially latching onto the genome of the virus and preventing it from making copies of itself, blocking infection. The findings are a promising step towards developing new drugs for combatting a wide range of immune system disorders.

The discovery was made by teams led by Bhushan Nagar, a professor in the Department of Biochemistry at McGill's Faculty of Medicine, and Dr. Giulio Superti-Furga at the CeMM. Building on the 2011 CeMM discovery by Dr. Andreas Pichlmair that IFIT proteins unexpectedly interact directly with the viral RNA to inhibit its replication, the group's latest discovery reveals the molecular mechanism behind how IFIT proteins capture only the viral RNA and distinguishes it from normal molecules belonging to the host. Their research will be published on January 13 in the journal Nature.

"Infection by pathogens such as viruses and bacteria are caught by a layer of the immune system that consists of guard-like proteins constantly on the lookout for foreign molecules derived from the pathogen," explains Prof. Nagar. "Once the pathogen is detected, a rapid response by the host cell is elicited, which includes the production of an array of defender molecules that work together to block and remove the infection. The IFIT proteins are key members of these defender molecules."

When a virus enters a cell, it can generate foreign molecules such as RNA with three phosphate groups (triphosphate) exposed at one end, in order to replicate itself. Triphosphorylated RNA is what distinguishes viral RNA from the RNA found in the human host. During this time, the receptors of the innate immune system are usually able to detect the foreign molecules from the virus and turn on signaling cascades in the cell that leads to the switching on of an antiviral program, both within the infected and nearby uninfected cells. Hundreds of different proteins are produced as part of this anti-viral program, which work in concert to resist the viral infection.

In the Nagar lab, McGill graduate student Yazan Abbas used an arsenal of biophysical techniques, most notably X-ray crystallography, to capture the IFIT protein directly in the act of recognizing the foreign RNA. The work shed light on the interaction between IFITs and RNAs. The researchers determined that IFIT proteins have evolved a specific binding pocket, chemically compatible and big enough to fit only the triphoshorylated end of the viral RNA. Human RNA is not able to tightly interact with this pocket, thereby circumventing autoimmune reactions.

"Once the IFIT protein clamps down on the viral RNA, the RNA is then presumably prevented from being used by the virus for its own replication," says Superti-Furga, "Since many viruses, such as influenza and rabies, rely on triphosphate RNA for their lifecycle, these results have widespread implications in understanding how our cells interact with viruses and combat them."

This work could help advance the development of new drugs for combating a wide array of immune system disorders. "Our findings will be useful for the development of novel drugs directed at IFIT proteins, particularly in cases where it is necessary to dampen the immune response, such as inflammation or cancer therapy," says Nagar.


Story Source:

The above story is based on materials provided by McGill University. Note: Materials may be edited for content and length.


Journal Reference:

  1. Yazan M. Abbas, Andreas Pichlmair, Maria W. Gσrna, Giulio Superti-Furga & Bhushan Nagar. Structural basis for viral 5′-PPP-RNA recognition by human IFIT proteins. Nature, 13 January 2013 DOI: 10.1038/nature11783

Cite This Page:

McGill University. "Foot soldiers of the immune system." ScienceDaily. ScienceDaily, 13 January 2013. <www.sciencedaily.com/releases/2013/01/130113144927.htm>.
McGill University. (2013, January 13). Foot soldiers of the immune system. ScienceDaily. Retrieved July 23, 2014 from www.sciencedaily.com/releases/2013/01/130113144927.htm
McGill University. "Foot soldiers of the immune system." ScienceDaily. www.sciencedaily.com/releases/2013/01/130113144927.htm (accessed July 23, 2014).

Share This




More Health & Medicine News

Wednesday, July 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Courts Conflicted Over Healthcare Law

Courts Conflicted Over Healthcare Law

AP (July 22, 2014) — Two federal appeals courts issued conflicting rulings Tuesday on the legality of the federally-run healthcare exchange that operates in 36 states. (July 22) Video provided by AP
Powered by NewsLook.com
Why Do People Believe We Only Use 10 Percent Of Our Brains?

Why Do People Believe We Only Use 10 Percent Of Our Brains?

Newsy (July 22, 2014) — The new sci-fi thriller "Lucy" is making people question whether we really use all our brainpower. But, as scientists have insisted for years, we do. Video provided by Newsy
Powered by NewsLook.com
Scientists Find New Way To Make Human Platelets

Scientists Find New Way To Make Human Platelets

Newsy (July 22, 2014) — Boston scientists have discovered a new way to create fully functioning human platelets using a bioreactor and human stem cells. Video provided by Newsy
Powered by NewsLook.com
Gilead's $1000-a-Pill Drug Could Cure Hep C in HIV-Positive People

Gilead's $1000-a-Pill Drug Could Cure Hep C in HIV-Positive People

TheStreet (July 21, 2014) — New research shows Gilead Science's drug Sovaldi helps in curing hepatitis C in those who suffer from HIV. In a medical study, the combination of Gilead's Hep C drug with anti-viral drug Ribavirin cured 76% of HIV-positive patients suffering from the most common hepatitis C strain. Hepatitis C and related complications have been a top cause of death in HIV-positive patients. Typical medication used to treat the disease, including interferon proteins, tended to react badly with HIV drugs. However, Sovaldi's %1,000-a-pill price tag could limit the number of patients able to access the treatment. TheStreet's Keris Lahiff reports from New York. Video provided by TheStreet
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins