London researchers discover novel mechanism involved in key immune response

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."

Related Stories

Scientists shine new light on inflammatory diseases

Mar 16, 2008

Investigators at Hospital for Special Surgery have identified a new mechanism involved in the pathogenesis of inflammatory diseases such as rheumatoid arthritis. The mechanism may also shed some light on why gene therapy ...

Papillomavirus silences innate immune response

Dec 03, 2009

In the 1980s, Harald zur Hausen and his co-workers discovered that specific types of human papillomavirus (HPV) cause cervical cancer. Scientists soon found out how these pathogens cause cells to degenerate. ...

Recommended for you

Profilin can induce severe food-allergic reactions

14 hours ago

(HealthDay)—Profilins are complete food allergens in food-allergic patient populations that are exposed to high levels of grass pollen, according to a study published in the December issue of Allergy.

Structured education program beneficial for anaphylaxis

Nov 21, 2014

(HealthDay)—A structured education intervention improves knowledge and emergency management for patients at risk for anaphylaxis and their caregivers, according to a study published online Nov. 19 in Allergy.

Every step you take: STING pathway key to tumor immunity

Nov 20, 2014

A recently discovered protein complex known as STING plays a crucial role in detecting the presence of tumor cells and promoting an aggressive anti-tumor response by the body's innate immune system, according to two separate ...

User 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.