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Medium Breakthrough: New finding could lead to a treatment against EBV

Waverunner

Senior Member
Messages
1,079
It seems that EBV can trigger infected cells to lose expression of the iNKT cell receptor ligand CD1d and therefore makes infected cells invisible to the immune system. Restoring CD1d expression by the use of an analog of retinoic acid lead to recognition of infected cells in an experiment.

Now the big question is, how we can increase CD1d expression in humans. Could we use what the scientists used?

http://www.sciencedaily.com/releases/2013/10/131012093040.htm

Oct. 12, 2013 — Development of a vaccine against Epstein-Barr virus (EBV) has taken a step forward with the Canadian discovery of how EBV infection evades detection by the immune system.
EBV causes infectious mononucleosis and cancers such as Hodgkin's lymphoma and nasopharyngeal carcinoma, which is the most common cancer in China, as well as opportunistic cancers in people with weakened immune systems. A member of the herpes virus family that remains in the body for life, the virus infects epithelial cells in the throat and immune cells called B cells.
The researchers discovered that the virus triggers molecular events that turn off key proteins, making infected cells invisible to the natural killer T (NKT) immune cells that seek and destroy EBV-infected cells.
"If you can force these invisible proteins to be expressed, then you can render infected cells visible to NKT cells, and defeat the virus. This could be key to making a vaccine that would provide immunity from ever being infected with EBV," says Dr. Rusung Tan, the study's principal investigator. Dr. Tan is a scientist and director of the Immunity in Health & Disease research group at the Child & Family Research Institute at BC Children's Hospital, and a professor in the Department of Pathology at the University of British Columbia.
The findings were published this week in the print edition of the scientific journal Blood.
For this study, the researchers looked at cells from infected tonsils that had been removed from patients at BC Children's Hospital by Dr. Frederick Kozak. The researchers infected the tonsillar B cells with EBV, and then combined some of these cells with NKT cells. They found that more NKT cells led to fewer EBV-infected cells, while an absence of NKT cells was associated with an increase in EBV-infected cells.
 

PDXhausted

Senior Member
Messages
258
Location
NW US
Yes-- this is a big deal. Was just discussing this with my husband who is a lymphoma/leukemia doc. In the study they use AM580, a synthetic retinoic acid receptor-alpha agonist to induce CD1d expression and cell mediated death of EBV infected cells via NK/T cell recognition. There is a synthetic drug called ATRA that is used to treat certain leukemias with retinoic acid receptor over expression due to genetic translocation t(15;17). Has anyone ever used this?

I also wonder how similar accutane is to these? I also wonder--- if NK cells are already low in quantity or function, how effective would it be for them to recognize EBV anyway?
 

Waverunner

Senior Member
Messages
1,079
Yes-- this is a big deal. Was just discussing this with my husband who is a lymphoma/leukemia doc. In the study they use AM580, a synthetic retinoic acid receptor-alpha agonist to induce CD1d expression and cell mediated death of EBV infected cells via NK/T cell recognition. There is a synthetic drug called ATRA that is used to treat certain leukemias with retinoic acid receptor over expression due to genetic translocation t(15;17). Has anyone ever used this?

I also wonder how similar accutane is to these? I also wonder--- if NK cells are already low in quantity or function, how effective would it be for them to recognize EBV anyway?


What you said is super interesting. I didn't know about ATRA. Regarding the NK cells it is my pure guess, that even if numbers are low, as soon as they can recognize infected cells, the situation should improve in the long run.
 

Firestormm

Senior Member
Messages
5,055
Location
Cornwall England
I am not able to properly consider this - and can't gain access to the research article - in light of recent findings relating to EBV etc.

Press Release:
Child & Family Research Institute

Immune system discovery could lead to EBV vaccine to prevent mono, some cancers

October 11, 2013

Development of a vaccine against Epstein-Barr virus (EBV) has taken a step forward with the Canadian discovery of how EBV infection evades detection by the immune system.

EBV causes infectious mononucleosis and cancers such as Hodgkin’s lymphoma and nasopharyngeal carcinoma, which is the most common cancer in China, as well as opportunistic cancers in people with weakened immune systems.

A member of the herpes virus family that remains in the body for life, the virus infects epithelial cells in the throat and immune cells called B cells.

The researchers discovered that the virus triggers molecular events that turn off key proteins, making infected cells invisible to the natural killer T (NKT) immune cells that seek and destroy EBV-infected cells.

“If you can force these invisible proteins to be expressed, then you can render infected cells visible to NKT cells, and defeat the virus. This could be key to making a vaccine that would provide immunity from ever being infected with EBV,” says Dr. Rusung Tan, the study’s principal investigator.

Dr. Tan is a scientist and director of the Immunity in Health & Disease research group at the Child & Family Research Institute at BC Children’s Hospital, and a professor in the Department of Pathology at the University of British Columbia.

The findings were published this week in the print edition of the scientific journal Blood.

For this study, the researchers looked at cells from infected tonsils that had been removed from patients at BC Children’s Hospital by Dr. Frederick Kozak.

The researchers infected the tonsillar B cells with EBV, and then combined some of these cells with NKT cells. They found that more NKT cells led to fewer EBV-infected cells, while an absence of NKT cells was associated with an increase in EBV-infected cells.

This research was funded by the Canadian Institutes of Health Research SLED Team for Childhood Autoimmunity, and BC Children’s Hospital Foundation. Dr. Tan is a Michael Smith Foundation Senior Scholar.

Read more:

I think that, for me, this is less about the possible development of a vaccine and more about how EBV might fool the immune system.

There has been a lot said about EBV and ME. I'm really not sure what the implications of this might be - there could be none. Need to read the research I think...
 

Soundthealarm21

Senior Member
Messages
420
Location
Dallas, TX
It seems like this could turn into a huge breakthrough if I'm reading into it correctly! Finding out what is causing the problem is the first step and that seems to have been found. Now it's creating the solution.
 

Ema

Senior Member
Messages
4,729
Location
Midwest USA
More on retinoid based therapies for EBV infected B cells in this article (which can be found in the appropriate location).

http://bloodjournal.hematologylibrary.org/content/122/15/2600.abstract

Retinoid-based therapies are currently used clinically to treat a wide spectrum of diseases, and ones having an activity resembling AM580 may prove valuable for targeting the immune system toward EBV- infected B cells.

These include all-trans retinoic acid for promyelocytic leukemia48 and 9-cis retinoic acid for Kaposi’s sarcoma.48,49 The exact mechanisms that make these drugs effective are not completely known and, in addition to their ascribed roles, may involve the action of iNKT cells.