Solving the MS jigsaw puzzle: EBV, genetics and UV on MS risk

Professor David Nolan

Murdoch University, WA

January 2015

specialisation: Immunology

focus area: Causes and Prevention

funding type: Project

project type: Investigator Led Research

Summary

The Epstein-Barr virus (EBV) is a virus that causes glandular fever. Infection with the EBV appears to contribute to the development of MS, and this project aims to provide insights into how this occurs. This study will investigate blood cells and use novel laboratory techniques to identify those cells infected with EBV, and determine their influence on the activity of immune cells in the blood.

Professor David Nolan and his team will examine the effect of antibodies against EBV on specific immune cells. These antibodies are increased in people with MS, and Professor Nolan will investigate if they play a role in directing immune cells to target and damage the nerve cells in the central nervous system, or cause immune cells to harm the body.

The ability to identify EBV-infected cells in blood samples is an important and novel opportunity and hopefully will provide powerful new insights into the causes of MS and help to guide the development of new monitoring and treatment strategies.

Progress

The project plan originally planned to investigate the effects of EBV on the development of MS using a new technique called SmartFlare RNA detection and then planned to use a microscopy technique called confocal microscopy to validate the findings.

Unfortunately, this research project among others, discovered that Smartflare, despite its anticipated potential, is incompatible with a cell sorting technique, called flow cytometry. The team then investigated and developed new methods to enable them to formally address the role that EBV-infected B cells potentially play in MS disease, and thus open the way for novel diagnostic and therapeutic strategies.

Professor Nolan and colleagues have been able to successfully identify B cell subsets from people with MS and those without MS and have validated a standardised and reproducible approach to measuring different types of B cells. They have also been able to identify and measure proteins produced in response to EBV infection. Working with Dr Rakesh Veedu from Monash University, the team have now moved on to using a newer technology – aptamer molecular beacons to detect protein fragments in living cells.

They have also determined that the SmartFlare technique will be useful for the confocal microscopy analysis planned for the second stage of the process and will allow the team to identify EBV in latency in people with MS and people without MS.

publications

Tschochner M, Leary S, Cooper D, Strautins K, Chopra A, Clark H, Choo L, Dunn D, James I, Carroll WM, Kermode AG, Nolan D. (2016) Identifying patient-specific Epstein-Barr Nuclear Antigen-1 genetic variation and potential autoreactive targets relevant to multiple sclerosis. PLoS One 11(2): e0147567.

Updated: 20 April 2018

lead investigator

Dr David Nolan

total funding

$150,000

start year

2015

duration

2 years

STATUS

Past project

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Solving the MS jigsaw puzzle: EBV, genetics and UV on MS risk