MEA Summary Review: Is mystery factor in plasma causing viral immunity in ME/CFS? | 06 May 2020

May 6, 2020

Charlotte Stephens, Research Correspondent, ME Association.


There has been quite a bit of discussion over an interesting new study from a team of researchers at the University of California San Diego School of Medicine and 3 German Universities.

The study, published in the journal ‘ImmunoHorizons’ last week, is called:

Human Herpesvirus-6 Reactivation, Mitochondrial Fragmentation, and the Coordination of Antiviral and Metabolic Phenotypes in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Prof. Robert Naviaux and Dr. Bhupesh Prusty, who led the research, found that mitochondria in some ME/CFS patients may have undergone a switch, possibly triggered by HHV-6 reactivation, resulting in the mitochondria having antiviral properties, at the high cost of drastically decreased energy production. This switch may be caused by an unidentified factor in patient serum that can be transferred to healthy cells.

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“These findings are important because they show for the first time that there is an antiviral activity in the serum of patients with ME/CFS that is tightly associated with an activity that fragments the mitochondrial network and decreases cellular energy (ATP) production.

“This provides an explanation for the common observation that ME/CFS patients often report a sharp decrease in the number of colds and other viral infections they experience after they developed the disease.

“Our work also helps us understand the long-known, but poorly understood link of ME/CFS to past infections with Human Herpes Virus-6 (HHV-6) or HHV-7,” Professor Robert Naviaux.

Source: San Diego University Health.

Key Points

  • The researchers hypothesised that HHV-6 infection may play a role in ME/CFS as they found that HHV-6 reactivation in cells induces mitochondrial dysfunction and lowered cellular energy production.
  • They found that the decreased energy state in mitochondria can be induced in healthy cells by an unknown transferable factor secreted by HHV-6 reactivated cells.
  • They looked into HHV-6 as a potential causative factor for ME/CFS but found very low copies of viral genome in the 25 ME/CFS patients tested, which was not enough to point to any direct role of active viral infection.
  • Serum taken from ME/CFS patients and applied to healthy cells induced the same changes in the mitochondria and resultant antiviral properties in healthy cells as the unknown factor secreted from the HHV-6 reactivated cells.
  • The ME/CFS cells had antiviral properties, at the high cost of mitochondrial dysfunction and lowered energy production.
  • These serum experiments could be used to develop a diagnostic test and also be used to further study the mystery factor causing these changes.

Summary of findings and what they mean

This study shows that there is a transferable factor in the serum of people with ME/CFS that results in a level of immunity against certain types of viruses, but at the cost of decreased mitochondrial function, resulting in low energy production.

It found that both HHV-6 reactivation and ME/CFS patient serum treatment induced changes in mitochondrial structure and state (into defence mode instead of energy production mode), caused a hypometabolic state (reduced energy production) and a strong proinflammatory state in the cell that protects against certain viruses. Furthermore, the unknown factor that causes these changes is transferable to healthy cells under lab conditions.

The transferable factor in the serum is yet to be identified and so further studies are needed in order to isolate the factor that is causing these cell changes. The authors offered some possible candidates; cytokines, autoantibodies, or broken mitochondrial DNA released by the fragmented mitochondria.

The effect that the ME/CFS serum had on healthy control cells was so significant and specific that it was able to distinguish ME/CFS patient’s serum from controls with high accuracy. This could have implications for developing a diagnostic test.

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