Thursday, 25 September 2014

Charcot Project: EBV in mIce

Frankenstein mice provides insights into the immunology of EBV infection. #MSBlog #MSResearch

"This study using a tansgenic mice, or Frankenstein mice, may of interest to those of you following the evolving story of EBV in MS. EBV does not have a non-human host; it is a virus that is human specific. Therefore to create an animal model you have to make the animal humanoid. In this case a mouse was created in the lab to have a human-like immune system that allows it be infected with EBV. The investigators then looked at the cellular immune responses to EBV; the so called CD8+ T cell responses. You may recall that Professor Pender has data suggesting MSers have a deficient CD8+ cytotoxic CD8+ T cell response to EBV. In this study they show that CD8+ are responsible for controlling the EBV virus viraemia in this animal model. Whether or not this is relevant to MS is a moot point, but does provide a model system for testing vaccines. The latter is clearly what we need to do the ultimate experiment; to whether or not EBV causes MS. If vaccinating high-risk people against EBV prevents them from developing MS then we will have proved that EBV is the cause of MS. This is similar to HPV and cervical cancer; vaccinating girls against this virus has resulted in a fall in incidence of cervical cancer, thus proving that HPV is a cause of cervical cancer."

"The following is a link to Professor Pender's post; it is one of the most popular all-time posts on this blog."

Guest Post: Professor Michael Pender - Multiple Sclerosis ..., 11 Feb 2014
Professor Michael Pender graduated from The University of Queensland in 1974 with First Class Honours in Medicine and a University Medal. Over the next six years he trained as a physician and neurologist at the Royal ...


Wesnes et al. Adoptive Transfer of EBV Specific CD8+ T Cell Clones Can Transiently Control EBV Infection in Humanized Mice. PLoS Pathog. 2014;10(8):e1004333. doi: 10.1371/journal.ppat.1004333

Background: Epstein Barr virus (EBV) infection expands CD8+ T cells specific for lytic antigens to high frequencies during symptomatic primary infection, and maintains these at significant numbers during persistence. Despite this, the protective function of these lytic EBV antigen-specific cytotoxic CD8+ T cells remains unclear. 

Methods & Results: Here we demonstrate that lytic EBV replication does not significantly contribute to virus-induced B cell proliferation in vitro and in vivo in a mouse model with reconstituted human immune system components (huNSG mice). However, we report a trend to reduction of EBV-induced lymphoproliferation outside of lymphoid organs upon diminished lytic replication. Moreover, we could demonstrate that CD8+ T cells against the lytic EBV antigen BMLF1 can eliminate lytically replicating EBV-transformed B cells from lymphoblastoid cell lines (LCLs) and in vivo, thereby transiently controlling high viremia after adoptive transfer into EBV infected huNSG mice. 

Conclusions: These findings suggest a protective function for lytic EBV antigen-specific CD8+ T cells against EBV infection and against virus-associated tumors in extra-lymphoid organs. These specificities should be explored for EBV-specific vaccine development.

1 comment:

  1. Pender and Giovannoni are spot on with evb been the cause of ms. My brother took artusenate for it's anti ebv and hv-6 qualities and has had considerable sustained improvements thank god for your pioneering hard work :)

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