Corporate Banner
Satellite Banner
Technology
Networks
Scientific Communities
 
Become a Member | Sign in
Home>News>This Article
  News
Return

A Comparative Medicine Study by Penn Vet Identifies a New Approach to Combat Viral Infections

Published: Thursday, November 15, 2012
Last Updated: Thursday, November 15, 2012
Bookmark and Share
When a virus such as influenza invades our bodies, interferon proteins are among the first immune molecules produced to fight off the attack.

Interferon can also play a role in suppressing tumor growth and the effects of autoimmune diseases, and doctors may use an artificial form of interferon to treat patients with certain cancers or multiple sclerosis. But even this approach sometimes fails when patients’ bodies reject the foreign interferon or growing resistant to its effects.

A study by scientists from the University of Pennsylvania School of Veterinary Medicine offers a new strategy for enhancing the effects of interferon in fighting off infection. The research suggests that, by targeting a particular molecule in the interferon signaling pathway, specially designed drugs may be able to boost the activity of a person’s own interferon, augmenting the immune system’s fight against viruses. It’s possible that the same drugs might also be effective against some types of cancer and certain autoimmune conditions.

Serge Fuchs, a professor of cell biology in Penn Vet’s Department of Animal Biology and director of the School’s Mari Lowe Comparative Oncology Center, was the senior author on the paper published in the Proceedings of the National Academy of Sciences.

“The practical significance of our study is a demonstration of the ability to use emerging pharmaceuticals to reactivate an individual’s own interferon or to use a reduced dose to get the same effect,” Fuchs said.

Christopher Carbone and Hui Zheng of the Department of Animal Biology and John Lewis and Alexander Reiter of the Department of Clinical Studies played leading roles in the study. Additional Penn Vet collaborators were Sabyasachi Bhattacharya, Paula Henthorn and Kendra Bence. Zhong-Yin Zhang of Indiana University School of Medicine and Darren Baker of Biogen Idec also contributed.

The research would have been impossible without the team’s comparative-medicine approach, in which they examined the effects of activating the interferon pathway in both human cells and in cats affected by a naturally occurring disease. Mice would normally be the model organism of choice for such a study, but they lack a molecular element of the interferon pathway that humans and cats share.
“Mice are very convenient, but they may not always recapitulate human diseases that well,” Fuchs said. “Veterinary diseases happen naturally, and they provide a less convenient but a more truthful recapitulation of the human situation.”

Interferon fights viruses by binding to an interferon receptor on cells, triggering a cascade of other molecular events and leading to the production of proteins that prevent viruses from reproducing or that stimulate other immune responses. But because too much interferon can harm the host’s body, this signaling cascade has a built-in brake: Using a separate molecular pathway, interferon triggers the body’s cells to remove its own receptor, so the immune system attack doesn’t go on indefinitely.
“It’s very important to understand what regulates the responsiveness of cells to interferon, and a major factor is the levels of cell-surface receptors,” Fuchs said.

Although the researchers’ investigations of these pathways led them to identify a target for improving the body’s virus-fighting ability, they didn’t set out to discover a drug. Rather, they were attempting to solve a paradox of cell biology.

The paradox rests on the fact that many steps in the interferon-signaling pathway involve adding a molecule of phosphate to proteins in the cascade. Interferon itself promotes the addition of phosphate onto the interferon receptor, yet previous evidence suggested that the receptor resisted being removed by the cell if it had phosphate added. Given that interferon does in fact trigger the removal of its own receptor, the research team hypothesized that another enzyme must be at work in the pathway to remove the phosphate molecule from the receptor so it could be consumed by the body’s cells to ramp down the immune-system response to viruses.

Performing a screening for this putative enzyme, they identified protein tyrosine phosphatase 1 B (PTP1B) as a likely candidate. In a series of experiments, the researchers confirmed that blocking PTP1B decreased the removal of the interferon receptor. As a result, interferon signaling became enhanced. Using human cells infected with hepatitis C, the researchers found that adding a PTP1B inhibitor allowed smaller doses of interferon to be effective in keeping the virus from reproducing. They demonstrated a similar effect in human cells infected with vesicular stomatitis virus.

Aiding in their work was the fact that pharmaceutical companies have already designed multiple drugs that inhibit the activity of PTP1B but for a completely separate reason than the enzyme’s involvement in interferon signaling.

“PTP1B also works on the leptin receptor,” Fuchs said. “This is the pathway that regulates satiety, appetite and weight gain. So in the past 10 years there have been massive industrial and academic undertaking to develop PTP1B inhibitors to treat obesity and diabetes.”

To see how these PTP1B inhibitors would impact viral infections in a living organism, the researchers could not use mice because mice lack a portion of the receptor that PTP1B acts upon, and so blocking PTP1B does not impact interferon signaling in the same way as it does in humans and other mammals. Instead, they examined five cats that had been enrolled by their owners in the study. Each was suffering from chronic stomatitis, a condition that involves substantial inflammation in the mouth and makes it painful for the cats to eat and groom. The cats received a single injection of a PTP1B inhibitor. Two weeks later, all five showed noticeable reductions in redness and inflammation, providing clinical evidence that these drugs could be used to treat infection.

Fuchs said that what seemed like a drawback in the study — that it couldn’t be effectively modeled in mice — ended up being a benefit, as naturally occurring diseases in animals such as cat and dogs more closely mimic many human diseases.

Because interferon is known to suppress tumors and help multiple sclerosis patients, the results of this study give the researchers optimism that PTP1B could be a target for anti-cancer and anti-autoimmune disease therapies.

As a next step, they plan to test the PTP1B inhibitors in a model of feline immunodeficiency virus, or the cat version of AIDS, to see if its virus-fighting capabilities can have an effect against that infection.


Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 3,000+ scientific posters on ePosters
  • More Than 4,500+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Testing Non-Breast/Ovarian Cancer Genes
Researchers have found that expanding gene panel beyond breast/ovarian cancer genes in these patients does not add any clinical benefit. Instead, testing has produced more questions than answers.
Saturday, May 21, 2016
How Did The Giraffe Get Its Long Neck?
Clues about the evolution of the giraffe’s long neck have now been revealed by new genome sequencing.
Wednesday, May 18, 2016
New Pathway That May Trigger Asthma Discovered
Finding could lead to better drugs for the many asthma patients who don’t respond well to current medications.
Wednesday, April 20, 2016
Parkinson's "Good" Genotype Makes Less of "Bad" Protein
Penn study uncovers genetic variation that predicted type and rate of physical decline in patients with Parkinson's disease.
Friday, April 15, 2016
Revealing the Function of Mysterious RNAs
Study co-led by Penn Medicine researcher shows non-coding DNA acting as enhancer of nearby gene's expression.
Tuesday, April 12, 2016
Seeing Cell to Cell Differences
Seeing differences between individual cells for first time explains symptoms of rare genetic disorders, finds penn study.
Tuesday, April 05, 2016
Countless New, Cleaner Uses of Methane
Chemists have demonstrated the potential to use methane as a versatile chemical building block with which to make more complex molecules.
Tuesday, March 29, 2016
Mechanism Explains Female Bias in Autoimmunity

Tuesday, March 22, 2016
Model Sheds Light on Human Genome Variability
Fresh approach identifies genetic risk factors that influence complex human diseases
Tuesday, February 23, 2016
Machine Learning Uncovers Unknown Bacterial Features
Technique robustly identified characteristic gene expression patterns in response to antibiotics, low oxygen conditions.
Monday, January 25, 2016
Genetic Cause of Heart Disease
Penn study sheds light on a genetic cause of heart disease.
Wednesday, December 16, 2015
Gene Pair Plays Crucial Role in Colon Cancer
In a new study researchers from the University of Pennsylvania describe two related genes in the Musashi family that are required for colon cancer to develop, and that may be useful targets for effective treatment.
Monday, December 07, 2015
Penn Engineering Team Showcases ‘Eye-on-a-Chip’ Technology
These small plastic chips contain microfluidic channels, carefully designed so that human cells can grow in them in a way that simulates the three-dimensional environments they would normally inhabit in the body.
Thursday, November 19, 2015
How Different Treatments for Crohn's Effect the Microbiome
Different treatments for Crohn's disease in children affects their gut microbes in distinct ways, which has implications for future development of microbial-targeted therapies for these patients, according to a study led by researchers from the Perelman School of Medicine at the University of Pennsylvania.
Friday, October 16, 2015
Profiling Non-Protein-Coding RNAs
Growing insights about a significant, yet poorly understood, part of the genome – the “dark matter of DNA” -- have fundamentally changed the way scientists approach the study of diseases.
Wednesday, October 14, 2015
Scientific News
The Rise of 3D Cell Culture and in vitro Model Systems for Drug Discovery and Toxicology
An overview of the current technology and the challenges and benefits over 2D cell culture models plus some of the latest advances relating to human health research.
World’s Largest Coral Gene Database
‘Genetic toolkit’ will help shed light on which species survive climate change.
A Boost for Regenerative Medicine
Growing tissues and organs in the lab for transplantation into patients could become easier after scientists discovered an effective way to produce three-dimensional networks of blood vessels, vital for tissue survival yet a current stumbling block in regenerative medicine.
Breast Cancer Drug Hope
A drug for breast cancer that is more effective than existing medicines may be a step closer thanks to new research.
Untangling Disease-Related Protein Misfolding
Work advances understanding of genetic forms of thrombosis, emphysema, cirrhosis of the liver, neurodegenerative diseases and inflammation, among others.
Early Genetic Changes in Premalignant Colorectal Tissue Identified
Findings point to drivers of early cancer development, targets for cancer prevention therapies.
Harnessing Nature’s Vast Array of Venoms for Drug Discovery
Scripps scientists have developed a method for rapidly identifying venoms.
Scientists Find Evidence That Cancer Can Arise Changes
Researchers at Rockefeller University have found a mutation that affects the proteins that package DNA without changing the DNA itself can cause a rare form of cancer.
Developing a More Precise Seasonal Flu Vaccine
During the 2014-15 flu season, the poor match between the virus used to make the world’s vaccine stocks and the circulating seasonal virus yielded a vaccine that was less than 20 percent effective.
A Peachy Defense System for Seeds
ETH chemists are developing a new coating method to protect seeds from being eaten by insects. In doing so, they have drawn inspiration from the humble peach and a few of its peers.
Scroll Up
Scroll Down
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
3,000+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,500+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!