New insights into MS disease mechanismsTuesday, June 10, 2008, 17:45 - 18:00
Detection of viruses in multiple sclerosis using the human panviral diagnostic array G. Trillo-Pazos, A. Khan, P. Kellam, R. Reynolds, J. Bell, R. Weiss, D.H. Miller (London, Edinburgh, GB)
Objective: To determine if MS has a viral aetiology, we designed and developed a novel Human Panviral Diagnostic Array (HVDA) to test for the presence of viruses in human post-mortem brain tissue samples.
Methods: The HVDA was designed using a biological approach to detect latent and lytic infection by 210 viruses in human clinical samples. Total RNA was extracted from 6 post-mortem MS cases; 4 control cases with dementia; 4 samples with clinical viral HIV or Hepatitis B infection and hybridised to our array using standard Agilent array protocols. Array data was analysed using the SPSS v12 WIN statistics platform up-regulated viral probes were identified with ANOVA at p< 0.05 compared to negative controls.
Results: With the HVDA we detected a “common” viral pattern of infection consisting of endogenous retroviruses, latent herpesvirus infection and other viruses across the tissue samples tested. We were able to detect HIV, hepatitis B and EBV infection in those cases with clinically diagnosed viral infection prior to death. No single virus has being exclusively associated with MS in our samples so far. These results have being verified by RT-PCR. These findings suggest that there is an apparent “viral ecosystem” present in human tissues independent of disease.
Conclusion: This HVDA can detect clinically diagnosed viral diseases in human tissue samples and an apparent background “viral ecosystem”. However, specific detection of viruses depends on issues of levels of infection (i.e. copy number) and the brain is a complex cellular system that is refractive to widespread viral infection. To address this, we are currently testing the “hit and run” mechanism of viral infection by using a microgenomics approach in MS.