See:
http://www.alphagalileo.org/ViewItem.aspx?ItemId=123271&CultureCode=en
Cannot copy the text of the article.
It says they found EBV can inactivate a cytokine, human CSF-1, which is essential for innate and adaptive Immunity against viral and microbial infections, and cancer.
They used 3d images to atomic resolution of how BARF1 captures and inactivates Human CSF-1, and to unravel moleculair mechanism of this inactivation.
(Found on MEnet)
Thanks Spring. I've copied it out below
Ghent University scientists discover the mechanism of inactivation of a human cytokine important for immunity by the Epstein-Barr Virus
20 August 2012
Ghent University
http://www.alphagalileo.org/ViewItem.aspx?ItemId=123271&CultureCode=en
Viruses co-evolved with their mammalian hosts by developing sophisticated interactions with host molecular targets that primarily serve to evade detection and elimination by the immune system.
This is well reflected in strategies based on the secretion of viral protreins aiming to neutralize the activity of host cytokines and chemokines that are produced to mobilize immune system cells to areas of infection and to orchestrate an appropriate immune response.
Understanding the molecular repertoire and strategies employed by global viral pathogens is especially important at a time when large-scale studies continue to uncover the genetic and proteomic diversity of viruses.
The Epstein-Barr Virus (EBV) is truly a global human pathogen that establishes life-long persistent infections in 90-95% of the human population, highlighting the fact that EBV must employ a very effective strategy in order to subvert detection and elimination by the human immune system.
EBV is the causative agent for infectious mononucleosis (KLIERKOORTS), several lymphatic malignancies (
e.g. Burkitt’s and Hodgkin’s lymphomas), and gastric and nasopharyngeal carcinomas (NPC).
A striking aspect of the EBV proteomic pool concerns the secretion the protein BARF1, which in recent years was shown to be highly associated with epithelial malignancies such as nasopharyngeal carcinoma (NPC) and gastric carcinomas.
The discovery that BARF1 is a binding protein for the essential hematopoietic cytokine hCSF-1 and that it can block monocyte proliferation established a link to the possible immunomodulatory role of BARF1.
This is because the target for BARF1, the human cytokine CSF-1, is essential for innate and adaptive immunity against viral and microbial infections, and cancer.
However, the structural and molecular basis of how BARF1 sequesters and inactivates CSF-1 had remained unknown for nearly two decades.
By employing an interidisciplinary approach combining structural biology, biophysics, biochemistry, molecular and cellular biology, we succeeded in obtaining 3D images to atomic resolution of how BARF1 captures and inactivates human CSF-1, and to unravel the molecular mechanism of this inactivation.
The most far-reaching dimension of our work is the uncovering of a unique mechanism for the inactivation of a human growth factor by a viral decoy receptor to achieve immunomodulation. BARF1 is structurally different from the cognate receptor for hCSF-1 and evolved to target a novel binding epitope at the dimer interface of hCSF-1 distinct from the cognate receptor binding site.
Our discovery adds an important piece to the puzzle of how creatively viruses can evade the human immune system and offers opportunities to exploit such insights for therapeutic purposes.
Importantly, we are reminded that the future may hold many such surprises regarding viral strategies to subvert the human immune system.
In other words, we may have only scratched the tip of the iceberg!
