Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Infection warning system in cells contains targets for antiviral and vaccine strategies

31.07.2012
Findings point to enhancing the role of RGI-I pattern recognition receptors in detecting viruses and alerting an immune response

Two new targets have been discovered for antiviral therapies and vaccines strategies that could enhance the body's defenses against such infectious diseases as West Nile and hepatitis C. The targets are within the infection warning system inside living cells.

No vaccines exist for the viruses that cause West Nile or hepatitis C. New therapies are urgently needed to prevent and treat serious infections by these and related viruses.

The University of Washington is engaged in a major, multipronged effort to design therapeutics that harness the warning signals the body produces when viruses attack. Such therapies would prod people's cells into launching a stronger counterattack to control infections by elusive viruses.

UW specialists in how the body fends off viral diseases are studying pattern recognition molecules, called RIG-I-like receptors, found inside living cells. When these receptors detect virus invasions, they call in the immune system to fight infection.

Scientists in the laboratory of Dr. Michael Gale, Jr., UW professor of immunology, observed an interaction between these molecular dispatchers and a protein called 14-3-3 epsilon This protein acts a docking station where other proteins can gather. There they can more efficiently send out signals in response to threats.

The researchers noticed that the interaction between the alert trigger (RIG-I) and the docking station (14-3-3 epsilon) steps up when cells were infected with virus. The agitation prompts RIG-I to work with other proteins, such as TRIM25. Those proteins are essential for RIG-I to warn the immune system to respond to a virus intruder.

"Our work also demonstrated that RIG-I binding to 14-3-3 epsilon is important for RIG-I to move from within the cell where it detects viral RNA to a location on the cell's membrane where the cell's antiviral defenses can be activated," said Dr. Helene Liu, a postdoctoral fellow who led the study. The move is somewhat like running from the inner corridors of a building to a window to call for help.

"By understanding the molecular partners and location changes that RIG-I requires to convey its signal that virus is present in a cell, we can start to design therapeutics that can trigger this process to kick-off an antiviral immune response and fight virus infection," Liu said.

The scientists reported these initial findings in the May 17 issue of Cell Host & Microbe. The Gale laboratory reports additional observations on the RIG-I-like receptors in the August issue of Immunity, published online July 26.

Postdoctoral fellows Dr. Mehul Suthar and Dr. Hilario Ramos found that, during West Nile virus infection, an RIG-I like receptor called LGP2 promotes the survival and activity of CD8+ T white blood cells, commonly called killer T cells. These disease-fighters eliminate virus-infected cells from the body.

"By increasing the ability and length of time CD8+T cells can work within the body when West Nile virus is present, the immune system is strengthened and has a better chance of eliminating the virus," Suthar commented. Ramos added, "Based on this work, we can consider new ways to boost vaccine effectiveness through design of adjuvants or immune-stimulants. These might be applied within a vaccine approach to regulate LGP2 to enhance immunity to infection."

Gale directed the research effort for both projects. He heads the Center for Study of Innate Immunity to Hepatitis C Virus and the Center for Immune Mechanisms of Flavivirus Control, as well as two National Institutes of Health-funded multi-million dollar programs to develop new antiviral therapies and vaccine adjuvants.

"These two new discoveries," Gale said, "greatly advance our knowledge of how the body senses and responds to virus infection and provide us with new avenues to explore when designing antiviral therapies and new vaccines.

"West Nile virus is an emerging virus that has spread across the United States, and hepatitis C virus infects over 170 million people globally. Both viruses are devastating to the health of the individuals they infect. That is why the development of new clinical resources such as vaccines and antivirals for each is so critical."

West Nile virus is spreading throughout North America through infected mosquitoes. It can cause paralysis and death in people. Hepatitis C virus is transmitted through contact with blood or blood products containing the virus. It causes swelling and inflammation of the liver.

Most hepatitis C infections are persistent because the virus evades the immune defenses that normally limit the course of disease. The virus generates a chronic liver inflammation which scars the organ's tissues. The scarring can lead to liver failure and increases the risk of liver cancer. While therapies are available to treat hepatitis C infections, these treatments have harsh side-effects and are not effective in all people. No antiviral therapies are available to treat people infected with West Nile virus.

The work that led to the recent discoveries in the Gale laboratory was funded by grants from the National Institute for Allergy and Infectious Diseases of the National Institutes of Health to study the body's immune responses to hepatitis C and West Nile virus infections.

Leila Gray | EurekAlert!
Further information:
http://www.uw.edu

More articles from Health and Medicine:

nachricht Underwater Snail-o-Bot gets kick from light
27.02.2020 | Max-Planck-Institut für Intelligente Systeme

nachricht Existing drugs may offer a first-line treatment for coronavirus outbreak
27.02.2020 | Norwegian University of Science and Technology

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: High-pressure scientists in Bayreuth discover promising material for information technology

Researchers at the University of Bayreuth have discovered an unusual material: When cooled down to two degrees Celsius, its crystal structure and electronic properties change abruptly and significantly. In this new state, the distances between iron atoms can be tailored with the help of light beams. This opens up intriguing possibilities for application in the field of information technology. The scientists have presented their discovery in the journal "Angewandte Chemie - International Edition". The new findings are the result of close cooperation with partnering facilities in Augsburg, Dresden, Hamburg, and Moscow.

The material is an unusual form of iron oxide with the formula Fe₅O₆. The researchers produced it at a pressure of 15 gigapascals in a high-pressure laboratory...

Im Focus: From China to the South Pole: Joining forces to solve the neutrino mass puzzle

Study by Mainz physicists indicates that the next generation of neutrino experiments may well find the answer to one of the most pressing issues in neutrino physics

Among the most exciting challenges in modern physics is the identification of the neutrino mass ordering. Physicists from the Cluster of Excellence PRISMA+ at...

Im Focus: Therapies without drugs

Fraunhofer researchers are investigating the potential of microimplants to stimulate nerve cells and treat chronic conditions like asthma, diabetes, or Parkinson’s disease. Find out what makes this form of treatment so appealing and which challenges the researchers still have to master.

A study by the Robert Koch Institute has found that one in four women will suffer from weak bladders at some point in their lives. Treatments of this condition...

Im Focus: A step towards controlling spin-dependent petahertz electronics by material defects

The operational speed of semiconductors in various electronic and optoelectronic devices is limited to several gigahertz (a billion oscillations per second). This constrains the upper limit of the operational speed of computing. Now researchers from the Max Planck Institute for the Structure and Dynamics of Matter in Hamburg, Germany, and the Indian Institute of Technology in Bombay have explained how these processes can be sped up through the use of light waves and defected solid materials.

Light waves perform several hundred trillion oscillations per second. Hence, it is natural to envision employing light oscillations to drive the electronic...

Im Focus: Freiburg researcher investigate the origins of surface texture

Most natural and artificial surfaces are rough: metals and even glasses that appear smooth to the naked eye can look like jagged mountain ranges under the microscope. There is currently no uniform theory about the origin of this roughness despite it being observed on all scales, from the atomic to the tectonic. Scientists suspect that the rough surface is formed by irreversible plastic deformation that occurs in many processes of mechanical machining of components such as milling.

Prof. Dr. Lars Pastewka from the Simulation group at the Department of Microsystems Engineering at the University of Freiburg and his team have simulated such...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

70th Lindau Nobel Laureate Meeting: Around 70 Laureates set to meet with young scientists from approx. 100 countries

12.02.2020 | Event News

11th Advanced Battery Power Conference, March 24-25, 2020 in Münster/Germany

16.01.2020 | Event News

Laser Colloquium Hydrogen LKH2: fast and reliable fuel cell manufacturing

15.01.2020 | Event News

 
Latest News

Preserved and fresh – Neutrons show details of the freeze drying process

27.02.2020 | Life Sciences

Underwater Snail-o-Bot gets kick from light

27.02.2020 | Health and Medicine

Explained: Why water droplets 'bounce off the walls'

27.02.2020 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>