Posted on: Monday, 20 December 2010, 08:14 CST

(Ivanhoe Newswire) — Epstein-Barr virus (EBV) infects 90% of people at some point in their lives – and most will never know it.  However, HIV patients, receivers of organ transplants, and others with immune system problems may not be so lucky. EBV puts such people at a greater risk of cancer, and scientists are just discovering why.

Duke Cancer Institute researchers recently found a pathway used by infected cells to fight EBV infection, and may be able to use this discovery to better understand how the immune system responds to cancerous viruses.

"Using cell culture studies, we have uncovered a major pathway that the infected host cell activates to prevent an oncogenic virus from causing cancer," lead author of the study Michah Luftig, Ph.D, and Assistant Professor of Molecular Genetics and Microbiology was quoted as saying.  "We proposed that the cell was sensing that the virus is trying to take over.  When this oncogenic stress response is activated, it keeps the virus in check, and now we know why."

The research team studied the ways in which EBV can overtake cellular response, and hope that their findings will lead to the development of EBV-fighting therapies for those with weakened immune systems.  one key discovery is that two enzymes, called kinesis, stimulate the oncogenic stress response which typically fights EBV infection in strong immune systems (usually early in life).

In their study, the researchers blocked these kinesis, called ATM and Chk2, and observed an uncontrolled growth of infected cells.  they accumulated at ten times the typical amount, a large growth typically associated with many types of cancers, such as post-transplant lymphproliferative disorder.

"the findings can be extended to the general case of any oncogene being activated that might start the process of tumor formation," Luftig was quoted as saying.  "About 20 percent of all human cancers are caused by infectious agents, where about 80 percent of these infections are viral."

The human papilloma virus, for example, is a viral infection which is known to lead to cervical cancer.

EBV is a unique virus, affecting people in different ways.  Children aged four to five may first suffer mild illness symptoms.  Teenagers may develop mononucleosis and suffer much more acute symptoms such as chronic fatigue.  for those with immune problems, different types of lymphoma can form.

SOURCE: Duke University Medical Center, December 2010

Source: Ivanhoe Newswire

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Public release date: 15-Dec-2010 [ | E-mail | Share ] Contact: Mary Jane Goremary.gore@duke.edu919-660-1309Duke University Medical Center

DURHAM, N.C. ? about 90 percent of people are infected at some time in their lives with Epstein-Barr virus (EBV), usually with no ill effects. But individuals with compromised immune systems, such as people with organ transplants or HIV infection, have a greater risk of cancer occurring because of this virus.

Scientists at the Duke Cancer Institute have discovered a pathway that infected cells use to root out EBV infections, a finding that has implications for understanding the human response to cancer-causing viruses in general.

“Using cell culture studies, we have uncovered a major pathway that the infected host cell activates to prevent an oncogenic virus from causing cancer,” said senior author Micah Luftig, Ph.D., Assistant Professor of Molecular Genetics and Microbiology. “We proposed that the cell was sensing that the virus is trying to take over. When this oncogenic stress response is activated, it keeps the virus in check, and now we know why.”

The Luftig group also learned how the Epstein-Barr virus overcomes the cell’s response. “The findings may eventually yield therapies to benefit people who don’t have good immune systems and who need protection from a threatening EBV infection,” Luftig said.

This work appears in the Dec. 15 online issue of Cell Host and Microbe.

Very early in many people’s lives, there is a huge expansion of immune system B cells infected with EBV. But thanks to the oncogenic stress response and a strong immune system, the majority of these infected cells are killed off and the person remains healthy. Luftig and his group, including lead authors Pavel Nikitin and Chris Yan, found two enzymes, called kinases, which were critical in mediating this oncogenic stress response and preventing unchecked B-cell cell growth, called immortalization.

When the scientists blocked the ATM and Chk2 kinases, unchecked growth resulted in 10 times more infected cells. This burgeoning cell growth is related to several types of cancer, including post-transplant lymphoproliferative disorder, in which a transplant patient gets a form of lymphoma because of B-cell proliferation, and HIV-associated B-cell lymphomas among others.

“This finding can be extended to the general case of any oncogene being activated that might start the process of tumor formation,” Luftig said. “About 20 percent of all human cancers are caused by infectious agents, where about 80 percent of these infections are viral.” another example of a viral infection leading to cancer is the human papillomavirus, implicated in cervical cancer.

Epstein-Barr virus infection can mean different courses for different people. in children 4-5 years old, a first infection with the virus may cause a mild illness, but if this primary infection happens during adolescence, the person may suffer a case of mononucleosis with heavy fatigue and other symptoms. in immune-compromised people, the virus can do much worse damage and cause forms of lymphoma.

Other authors include Eleonora Forte, Alessio Bocedi, Jay Tourigny, Katherine Hu, Jing Guo, David Tainter and Elena Rusyn of the Duke Department of Molecular Genetics and Microbiology, and Amee Patel, Sandeep Dave and William Kim of the Duke Institute for Genome Sciences & Policy as well as Rob White and Martin Allday of the Imperial College London.

For more information about Luftig lab’s studies: mgm.duke.edu/faculty/luftig/index.htm

Funding for this study came from the American Cancer Society, the National Cancer Institute, the Duke Center for AIDS Research, the Duke Comprehensive Cancer Center, and Golfers Against Cancer.

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