London researchers discover novel mechanism involved in key immune response

June 13, 2012

A team of researchers at Lawson Health Research Institute and Western University have identified a novel way that a common virus, called adenovirus, causes disease. In doing so, they have discovered important information on one of the body's key immune responses. Their findings, published today in Cell Host & Microbe, may have implications for infectious diseases and cancer.

Adenovirus infections most often cause mild illnesses of the respiratory system, resulting in runny noses, coughs and sore throats. However, researchers have been interested in adenoviruses since the 1960s, when it was discovered that they can cause tumors in rodents. These tumors arise because adenovirus infected cells divide uncontrollably and escape the , which are hallmarks of cancer.

One key component of antiviral immunity is interferon. "Interferons are proteins made and released by cells in response to the presence of viruses, bacteria, parasites or cancers," says Dr. Joseph Mymryk, a scientist at Lawson and a tumor virologist at London Health Sciences Centre. "Adenovirus is completely resistant to interferon."

Past studies have identified some of the ways in which adenovirus overcomes the interferon response, but Dr. Mymryk and Greg Fonseca, PhD Candidate and lead author on the study, have identified a new mechanism that relies on changes in epigenetic regulation. Epigenetics is an emerging field of study which involves non-genetic factors that cause an organism's genes to express differently.

The production of interferons is responsible for the majority of symptoms commonly associated with viral infection including fever, chills, muscle aches, and malaise. When a cell is exposed to interferon it increases the production of about 300 cellular genes that defend the cell from infection. The researchers have discovered that interferon-regulated genes require a specific epigenetic modification called monoubiquitination of histone 2B (H2B) to work. "There is still much to learn about this modification, but our studies are the first to show that it is absolutely required for the interferon response," says Fonseca. "This finding was totally unanticipated."

"Each cell has thousands of different genes and they can all be regulated in weird and wonderful ways," says Dr. Mymryk. "The monoubiquitination of H2B specifically results in large increases in the transcription of genes. We found that the interferon response uses this modification for the rapid increases in gene transcription (which leads to gene expression) that are needed to change the cell environment to respond to and stop the viral infection. What the does is essentially block the formation of the complex that performs the monubiquitination of H2B, thereby blocking its function."

Although the medical consequences of adenovirus are typically modest, the study's findings have implications in a broad range of diseases because of how influential the interferon response is to how we respond to infectious diseases and cancer.

"Many cancers are non-responsive to interferon," says Fonseca. "If we can more fully understand the mechanism of interferon response, we may be able to better treat these cancers. Overall, many of the tricks adenovirus uses may be similar to those used by other viruses and cancer cells."

Explore further: Timing, duration of biochemical bugle call critical for fighting viruses

Related Stories

Timing, duration of biochemical bugle call critical for fighting viruses

June 13, 2012
Researchers have identified the primary player of the biochemical bugle call that musters the body's defenders against viral infection.

Study could help improve gene therapy for heart disease, cancer

October 12, 2011
A Loyola University Chicago Stritch School of Medicine study could lead to improved gene therapies for conditions such as heart disease and cancer as well as more effective vaccines for tuberculosis, malaria and other diseases.

Big picture of how interferon-induced genes launch antiviral defenses revealed

April 10, 2011
When viruses attack, one molecule more than any other fights back. Interferon triggers the activation of more than 350 genes, and despite the obvious connection, the vast majority have never been tested for antiviral properties. ...

Recommended for you

Does your child really have a food allergy?

July 24, 2017
(HealthDay)—Many people misunderstand what food allergies are, and even doctors can be confused about how to best diagnose them, suggests a new report from the American Academy of Pediatrics.

Genetic immune deficiency could hold key to severe childhood infections

July 18, 2017
A gene mutation making young children extremely vulnerable to common viruses may represent a new type of immunodeficiency, according to a University of Queensland researcher.

What are the best ways to diagnose and manage asthma?

July 18, 2017
What are the best ways to diagnose and manage asthma in adults? This can be tricky because asthma can stem from several causes and treatment often depends on what is triggering the asthma.

Large multi-ethnic study identifies many new genetic markers for lupus

July 17, 2017
Scientists from an international consortium have identified a large number of new genetic markers that predispose individuals to lupus.

Study finds molecular explanation for struggles of obese asthmatics

July 17, 2017
A large, bouquet-shaped molecule called surfactant protein A, or SP-A, may explain why obese asthma patients have harder-to-treat symptoms than their lean and overweight counterparts, according to a new study led by scientists ...

Team identifies potential cause for lupus

July 14, 2017
Leading rheumatologist and Feinstein Institute for Medical Research Professor Betty Diamond, MD, may have identified a protein as a cause for the adverse reaction of the immune system in patients suffering from lupus. A better ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.