SMCI 2016 Ramsay Team 5 Research Update

Dr. Bhupesh Prusty (Julius Maximilian University of Wurzburg, Germany) provided SMCI with a progress update on his Ramsay Award Program 2016 Team 5 project. Dr. Prusty discussed his progress to date, mitochondrial dynamics, and what brought him to the field of ME/CFS.

  1. How were you introduced to the world of ME/CFS?

I have long been working on human herpesviruses HHV-6 and HHV-7. There are numerous epidemiological studies linking HHV-6/HHV-7 and various human diseases including ME/CFS. However, thus far the molecular mechanism linking these common viruses to any human disease has remained obscure. Being a molecular virologist, solving this enigma has been the research goal that I have been working towards for the past several years. Some of my recent work identified mitochondrial modulation as a key phenotypic effect of HHV-6 activation. As mitochondrial dysfunction is the hallmark of ME/CFS and HHV-6/HHV-7 is associated with this, I developed an interest in the world of ME/CFS.

  1. What compelled you to apply your research experience with HHV-6 and viral reactivation to ME/CFS?

Research from my group identified the molecular mechanism underlying HHV-6 mediated mitochondrial damage and this is groundbreaking work involving viral small RNAs in regulation of host mitochondrial homeostasis. For a long time we have known that mitochondrial function is severely affected in ME/CFS. I believe that there is a pathogenic connection to this process and in my opinion HHV-6 presents an ideal model to take this hypothesis forward. I believe that the pathogenic mechanism we are studying might be conserved across the different viral infections associated with ME/CFS. We are working towards a complete understanding of this process. 

  1. What are some of the novel technologies you use in your work and what power do they have to discover mechanisms for mitochondrial modulation?

We use mitochondria itself as a tool to quantify its health and status. This brings us very close to understanding any effects on mitochondria. We use high-end microscopy like super resolution imaging to study mitochondrial dynamics, its fission-fusion dynamics and its functional quality. These are fantastic tools developed by other labs but we have fused them elegantly into our system. We have one of the finest cell culture models of HHV-6/HHV-7 latency. We have characterized viral activation in these cells. This allows us to bring in advanced mitochondrial microscopy into these cells and visualize changes in mitochondria directly upon viral activation.

  1. Is there a clinical application to this work, if successful?

Yes, that’s our ultimate goal. Our results will help us in developing a quantitative evaluation technique to understand mitochondrial health in ME/CFS patients. In addition, we hope to narrow down the key molecular events behind viral activation induced mitochondrial dysfunction, which can help us to design better and alternative treatment strategies for ME/CFS.

  1. If your research supports a link between mitochondrial dysfunction and HHV-6, will that help us in refining subtypes of ME/CFS?

Yes, we believe that HHV-6/HHV-7 might contribute to ME/CFS in a subset of patients. But we also believe that many other pathogens utilize similar techniques to alter mitochondrial function. It will then be possible to apply systematic screening of patients and offer similar (alternative) therapy for these subgroup(s) of ME/CFS patients. This is still a hypothesis. If proven correct, this can fill a large knowledge gap in the field of ME/CFS. 

  1. What can you share about progress to date in your study?

We have achieved two major goals. First, we have successfully dissected out the exact molecular mechanism behind HHV-6 mediated mitochondrial dysfunction. This is a very interesting piece of work. However, we faced a challenging task to link this to ME/CFS patients. We are not clinical centers but we managed to analyze a small number of ME/CFS patients (n=10) from Europe. We found HHV-6/HHV-7 in blood cells of 60% of these cases. However, the viral load was not enough to directly link the virus to the disease. I guess this is one of the reasons, the clinicians have been skeptical about linking ME/CFS to any infection. We overcame this hurdle by finding out that it is probably not necessary to have viral infection in every cell to cause mitochondrial dysfunction. It seems possible that one cell having viral activation can alter mitochondrial function in neighboring or even distant cells by secreting modulators outside the infected cell. We have been able to demonstrate this mechanism using our viral cell culture model as well as ME/CFS patient samples. This presents us a unique scenario to study role of HHV-6/HHV-7 in ME/CFS.

  1. Has the Ramsay Award funding been a helpful investment in your work?

Definitely. There is virtually no funding available within Europe to study role of HHV-6 in any disease. ME/CFS is still not considered an important human disease. Therefore, the Ramsay Award was a very timely help for us to take our work one step ahead. We hope to publish our work soon and this should help gather momentum in the scientific community, and open funding opportunities for this research topic.