Navigation Links
A single protein helps the body keep watch over the Epstein-Barr virus
Date:2/17/2012

Boston, Mass. Some 90 percent of people are exposed to the Epstein Barr virus (EBV) at some point in their life. Even though it is quickly cleared from the body, the virus can linger silently for years in small numbers of infected B cells. According to researchers at Children's Hospital Boston and the Immune Disease Institute (IDI), the immune system subdues the virus by watching for a single viral protein called LMP1, knowledge that has already helped suggest two new treatments for the EBV-fueled cancers seen in some immunosuppressed patients.

The study team, led by Klaus Rajewksy, MD, and Baochun Zhang, MD, PhD, of the Program in Cellular and Molecular Medicine at Children Hospital Boston and the IDI, reported their results online this week in the journal Cell.

While the immune system's T cells rapidly clear most EBV-infected B cells, about one in a million infected cells escapes destruction. Within these cells, the virus enters a latent phase, kept in check by the watchful eye of so-called memory T cells. This uneasy relationship usually holds steady the rest of a person's life, unless something such as infection with HIV or use of anti-rejection drugs following a transplant suppresses the immune system and breaks the surveillance. The virus can then reawaken and drive the development of B cell cancers like AIDS-associated B cell lymphoma and post-transplant lymphoproliferative disorder.

To better understand how the immune system maintains its watch and how the virus turns cells cancerous, Rajewsky and his team had generated a model mimicking latent EBV infection by engineering mice whose B cells contained an inducible version of viral LMP1. Researchers have long known that EBV needs LMP1 to turn B cells cancerous, but modeling this relationship in vivo had proven challenging.

"We had previously attempted to develop an animal model of LMP1 transformation of B cells," said Rajewsky, who recently moved to the Max Delbrck Center for Molecular Medicine in Germany, "but we had never been able to get the mice in our models to actually produce any mature B cells. The immune response against the LMP1-producing B cells was so robust that the cells were eliminated very early on."

Their breakthrough came when Zhang and colleagues reengineered the model to lack T cells. "The mice were initially fine, but succumbed within two to three months to aggressive B cell lymphomas," Rajewsky said. "The profile mimicked very closely what we see in immunosuppressed lymphoma patients." In additional experiments with Rajewsky's original model, the team eliminated the mice's T cells before activating the viral protein in B cells, sparking a similar but even more rapid fatal disease.

The team also made several observations with possible clinical application. First, they noted that in the mouse model the LMP1 producing B cells were being attacked by a specific kind of T cell called a CD4+ T cell. "Transplant patients who develop B cell lymphomas because they are immunosuppressed by their anti-rejection drugs are often treated with T cells that carry the CD8 marker," Rajewsky noted. "These results would argue for also considering CD4+ T cells for treatment."

Second, they found that tumors in the LMP1 producing mice often displayed targets recognized by another kind of immune cell called a natural killer (NK) cell. Seeing an opportunity, Rajewsky worked with cancer immunologist Glenn Dranoff, MD and colleagues at Dana-Farber Cancer Institute, to test a potential therapeutic agent that uses a portion of the NK cell activating receptor called NKG2D, fused to the stimulatory Fc portion of an antibody, a combination capable of activating and directing immune attack against tumor cells. In a transplantation model of LMP1-fueled lymphomas, the NKG2D-Fc fusion proved quite capable of reducing tumor growth and prolonging survival of the recipients.

"These preclinical results suggest administration of the NKG2D-Fc fusion protein, perhaps combined with treatment with CD4+ T cells, could benefit some patients with EBV-driven lymphomas," Rajewsky said. "What we can say with certainty, though, is that LMP1 is the immune system's primary surveillance trigger following EBV infection and clearance, knowledge that we think will open doors to additional treatment options."


'/>"/>
Contact: Erin Tornatore
erin.tornatore@childrens.harvard.edu
617-919-3110
Children's Hospital Boston
Source:Eurekalert

Related medicine news :

1. A single therapy slows multiple cancers
2. Widowers Who Stay Single Might Face More Mental Health Woes
3. Scientists capture single cancer molecules at work
4. Anti-estrogen combo better than single drug for hormone-sensitive breast cancer
5. Rice chemists cram 2 million nanorods into single cancer cell
6. New screening method can detect a range of clinical conditions from a single dried blood spot
7. Single dose of hallucinogen may create lasting personality change
8. Women have stronger immune systems than men and its all down to a single chromosome
9. Single parents and gay couples face rental housing discrimination: UBC study
10. Single vaccines to protect against both rabies and Ebola
11. Single flexible sigmoidoscopy screening associated with reduced colorectal cancer
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/26/2016)... ... June 26, 2016 , ... On June 10-11, 2016, A Forever ... Cereal Festival and World’s Longest Breakfast Table in Battle Creek, MI, where the rehabilitation ... as home to some of the world’s leading providers of cereal and other breakfast ...
(Date:6/25/2016)... ... June 25, 2016 , ... Experts from ... at AcademyHealth’s Annual Research Meeting June 26-28, 2016, at the Hynes Convention Center ... care topics including advance care planning, healthcare costs and patient and family engagement. ...
(Date:6/25/2016)... CA (PRWEB) , ... June 25, 2016 , ... As ... with Magna Cum Laude and his M.D from the David Geffen School of Medicine ... and returned to Los Angeles to complete his fellowship in hematology/oncology at the UCLA-Olive ...
(Date:6/24/2016)... Michigan (PRWEB) , ... June 24, 2016 , ... Those ... deal with these feelings, many turn to unhealthy avenues, such as drug or alcohol ... of Marne, Michigan, has released tools for healthy coping following a traumatic event. , ...
(Date:6/24/2016)... , ... June 24, 2016 , ... ... offering micro-osteoperforation for accelerated orthodontic treatment. Dr. Cheng has extensive experience with all ... brackets , AcceleDent, and accelerated osteogenic orthodontics. , Micro-osteoperforation is a revolutionary ...
Breaking Medicine News(10 mins):
(Date:6/24/2016)... 24, 2016  Collagen Matrix, Inc., ("Collagen Matrix") ... manufacturing of collagen and mineral based medical devices ... Bill Messer has joined the company ... leverage the growing portfolio of oral surgery, neurosurgery, ... Bill joins the Collagen Matrix executive team as ...
(Date:6/24/2016)... The Academy of Managed Care Pharmacy (AMCP) ... would allow biopharmaceutical companies to more easily share health ... and coverage decisions, a move that addresses the growing ... The recommendations address restrictions in the sharing of ... label, a prohibition that hinders decision makers from accessing ...
(Date:6/24/2016)... 24, 2016   Pulmatrix, Inc ., (NASDAQ: ... inhaled drugs, announced today that it was added to ... its comprehensive set of U.S. and global equity ... an important milestone for Pulmatrix," said Chief Executive Officer ... of our progress in developing drugs for crucial unmet ...
Breaking Medicine Technology: