EBV infection and the MS brain

Multiple sclerosis

By Mardi Chapman

22 Aug 2018

Professor Rajiv Khanna, QIMR

Professor Rajiv Khanna, QIMR Berghofer

Scientists are coming closer to describing the role of the Epstein-Barr virus (EBV) in multiple sclerosis (MS) and at the same time trialing immunotherapy against the virus.

New research has confirmed EBV infection can be demonstrated not just in MS brains but also in control brains without neurological disease. However there was much higher proportion of EBV-infected cells in MS patients than was seen in the controls.

Co-author Professor Rajiv Khanna told the limbic the meticulous study using gold standard techniques for detecting EBV-encoded RNA-1 and latent EBV infection helped clarify previously inconsistent findings.

“But what was more interesting was that a lot of EBV-infected cells were sitting right there in the chronic active plaques.”

Professor Khanna, a senior scientist in tumour immunology at QIMR Berghofer, said there were a number of theories about the exact role EBV might be playing in the brain.

“The original story was that the immune cells which react against EBV in the immune system might be directly causing the damage to the nervous system – by attacking not just EBV but also attacking the nervous system.”

“The other theory is that EBV-infected cells themselves get into the brain and cause the damage in a different way, by reacting against proteins expressed on the neuronal cells.”

“It’s not unusual to find EBV in the brain, whether you have MS or not,” he said.

However it was surprising and unusual to find CD138+ plasma cells in nonvascular regions of the MS brain.

“It remains unclear whether the extravasation of plasma cells into the parenchyma is dictated by EBV infection or whether MS pathogenesis involves extravasation of EBV-infected plasma cells deep into the tissue, potentially perpetuating the inflammatory response in MS,” the study said.

The study also found evidence the brain might respond differently to changes in the EBV life cycle with the latent virus more prevalent in MS brains and the lytic virus restricted to chronic MS lesions.

“Whether lytic EBV can modulate the MS brain microenvironment or whether the MS brain microenvironment (i.e., chronic plaques or chronic active plaques) can modulate the EBV life cycle (i.e., latent or lytic) warrants further investigation.”

Professor Khanna said the strongest risk factors associated with MS were smoking, vitamin D deficiency, EBV, particularly high antibodies against EBV, and the HLA-DR15 allele.

“With all those risk factors, the risk of MS goes up by 224 fold,” he said.

“EBV clearly has a role in the pathogenesis of MS but whether EBV plays a role in disease initiation, progression or persistence? That is also a question that we can’t answer.”

However clinical trials were moving ahead of fully understanding the mechanism.

“The future is to use a T-cell based immunotherapy to EBV to treat MS. The immunotherapy is targeting the virus and you are removing one of the critical players.”

He said a clinical trial had just finished, building on a 2014 case report in which a MS patient was given his own expanded immune cells against EBV. MS lesions in the brain reduced, there was an objective clinical response and the patient was able to go back to work.

Neurologist Professor Simon Broadley, from Griffith University’s School of Medicine, said the study didn’t add a lot of evidence in support of EBV’s role in MS.

“However, I think there is a very strong likelihood that EBV is the key to MS and a number of other autoimmune diseases and that either a vaccine or the anti-EBV T-cell approach will prove effective for MS.”

“However, until these treatments are tested we will not have a definitive answer. The vaccine is proving difficult to develop.”

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