Navigation Links
Mild-mannered metabolic helper rushes to fight invading viruses, researchers report
Date:5/7/2010

BOSTON, Mass. - Within cells, an ancient antiviral duo can deliver a one-two knockout to thwart invading viruses, report researchers who have just unmasked the cellular sidekick that throws the first punch. The findings mean scientists must rethink the design of antiviral immunity and how the body fends off viruses of all types, including influenza and HIV.

In the study, Children's Hospital Boston researchers found, mild-mannered organelles inside the cell known as peroxisomes can detect virus invasion signals and launch a limited antiviral offensive. Other organelles, the mitochondria, follow up with a more definitive antiviral counterattack.

"This is the first demonstration that peroxisomes are involved in immunity," said Jonathan Kagan, staff scientist in the gastroenterology division and senior author of the paper published May 6 in the online journal Cell. "This work has implications for our understanding of how we interact with infectious viruses and even bacteria."

The paper establishes a new function for peroxisomes as a cellular compartment that promotes a rapid response to viral infection. With this discovery, the researchers say, scientists need to look for other cellular parts that may do double duty as pathogen detectors. A larger volunteer army may be lurking in cells as needed for the innate immune system.

In a clinical implication, the findings suggest a new approach to rare and largely untreatable conditions known as peroxisome biogenesis disorders, Kagan said. In the most common manifestation, Zellweger syndrome, children suffer from major developmental abnormalities and die as infants. The milder disorders allow children to live into their teens. Many affected children die of lung infections such as pneumonia, which may arise from problems in the antiviral signaling scaffold due to the absence of peroxisomes, Kagan speculates. Previously, the disorders have been considered developmental and metabolic.

When they are not fighting invading microbes, peroxisomes are busy mopping up the potentially damaging free radical byproducts produced by their larger distant cousins, mitochondria, the power plants of the cell. In other house-keeping duties, peroxisomes also make and attach the lipids that grease the cellular machinery so proteins can slide into or through membranes. Both organelles grow, multiply, and shrink in response to metabolic demands.

Peroxisomes acquire their virus-fighting power from a cloak of mitochondrial antiviral signaling protein, or MAVS. Five years ago, MAVS proteins were discovered on mitochondria, a surprising location for which they were named, and shown to be vital to the immune system's ability to fight infections.

MAVS proteins are found in all cells in the body, Kagan said, but until now they were only known to be draped around mitochondria. The latest study started as a search for MAVS on peroxisomes, an idea born from recent reports of other proteins shared by peroxisomes and mitochondria. On a graduate studies sabbatical from Vienna, first author Evelyn Dixit stained cells for MAVS and found the proteins on peroxisomes.

Next, she observed, the same MAVS proteins activated different antiviral immune responses, depending upon the organelle they adorned. "The difference was that the antiviral response was quicker and transient when it originated from peroxisomes compared to mitochondria," Dixit said.

In another difference, the peroxisomal MAVS turned on a subset of antiviral genes without a secreting interferon. By contrast, mitochondrial MAVS triggers interferon production and release, which alerts both the cell and its neighbors to mount a larger immune response.

"Seeing interferon-stimulated genes but no interferon was at first quite aggravating," Dixit said. "We thought we did something wrong. Then we had to turn our thinking around 180 degrees and accept that it was not a mistake. Peroxisomal MAVS leads to interferon-stimulated genes while bypassing interferon secretion."

The differential response may be a way that different kinds of cells can customize their antiviral responses to the special needs of different tissues, Kagan suggests. For example, the interferon response shuts down protein synthesis, promotes inflammation, and causes a general toxic effect that some tissues may be able to handle better than others, such as the intestines.

Without interferon, peroxisomes could mount a limited response in sensitive tissues, such as nerves, eyes, or heart muscle. "We have speculated that certain tissues may only use mitochondria or only use peroxisomes," Kagan said.

"At the end of the day, we found antiviral signaling can occur from peroxisomes and from mitochondria," he said. "Only from the peroxisome do we see a rapid response, and that is sufficient to control viruses, but it cannot eliminate them. Signaling from both is needed to effectively knock them out."


'/>"/>

Contact: Bess Andrews
elizabeth.andrews@childrens.harvard.edu
617-919-3110
Children's Hospital Boston
Source:Eurekalert

Related medicine news :

1. New Study Demonstrates Novel Use of Metabolic Imaging to Locate Sperm in Infertile Men -- Non-Invasive Imaging Procedure May Replace Invasive Techniques such as Testicula
2. Pharmahelper Pleased To Recognize Online Pharmacy Practice Standards Announced By Google Adwords
3. With Rainy Season Looming, Florida Woman Rushes to Aid of Haitians
4. 'Animals' Keep Germs Away From Kids' Toothbrushes
5. Kool Smiles Offers Free Toothbrushes and Education to Day Care Centers Affected by Massachusetts Initiative Supporting Childrens Oral Care
6. New blood test may help in the fight against lung cancer
7. Federal Agencies to Study Causes of Firefighters' Cancers
8. Cambodia takes action in fight against substandard and counterfeit medicines
9. Cell study finds receptor can fight tamoxifen-resistant breast cancer cells
10. BLUE Buffalo Pet Food and PETCO Partner to Fight Pet Cancer During Pet Cancer Awareness Month
11. Carcinogen Found in Many "Natural" Skin Care Products, One Skin Care Specialist Fights Back
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/10/2016)... Calif. (PRWEB) , ... February 10, 2016 , ... ... Water Brand. There were three leading bottled water brand owners that topped the list ... that enhance connectivity and optimize conversion. The premier brand was Tibet 5100, a top ...
(Date:2/10/2016)... ... ... Dr. Jessica Barron, of Barron Family Dental in Thornton, Colorado , ... in the North Metro Denver area. The new dental practice focuses on comfort where ... in the most relaxing environment. , While some dental visits can create anxiety for ...
(Date:2/10/2016)... ... February 10, 2016 , ... Intalere’s ... together more than 200 of the country’s top healthcare executives to share insights ... true benefit of the Forum is the provider-centric perspective, experience, expertise and strategy ...
(Date:2/10/2016)... ... February 10, 2016 , ... Gout is like no other joint ... is often severe, with intense swelling and redness. It is triggered by the crystallization ... older adults are the most susceptible, according to the February 2016 issue of Harvard ...
(Date:2/10/2016)... (PRWEB) , ... February 10, 2016 , ... Armune ... Apifiny® across their network of laboratory service centers across the country. Launched in ... aid clinicians in the detection of prostate cancer. Apifiny order volume exceeded 3,000 tests ...
Breaking Medicine News(10 mins):
(Date:2/10/2016)... DIEGO , Feb. 10, 2016 ALSP, Inc. ... , MD as Consultant for Medical Affairs in preparation for ... Michael Pierschbacher , PhD, CEO, stated, "We are pleased ... We look forward to working with an individual of such ... We look forward to drawing deeply on his broad experience ...
(Date:2/10/2016)... , Feb. 10, 2016 Intouch Solutions, a ... identified an industry-wide trend regarding the evolution of ... organizations to efficiently deliver compelling sales presentations via ... and another in 2015, Intouch uncovered that while ... devices and DSAs, many are not using them ...
(Date:2/10/2016)... HALLANDALE, Fla. , Feb. 9, 2016  Until ... sagging were surgery or liposuction. Thankfully, the FDA approved ... freezing them to death. Coolsculpting was originally approved in ... to the thighs and now the chin. With this ... Wellness Center can use a smaller applicator, the CoolMini, ...
Breaking Medicine Technology: