HHV-6 found in postmortem study of myalgic encephalomyelitis/chronic fatigue syndrome

Human herpesvirus 6 (HHV-6) and Epstein-Barr virus both have been linked to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), largely through studies of blood.  However, theories about the pathogenesis of ME/CFS focus on infection of the brain and spinal cord by these neurotropic viruses, and studies of the viruses in the blood may not reflect their activity in the brain and spinal cord.

Investigators at the University of Wurzburg in Germany and at Ohio State University led by Bhupesh Prusty examined brain and spinal cord obtained from postmortems of three patients with ME/CFS and 24 control subjects with other diseases. Using fluorescence in situ hybridization (FISH), they probed tissue for HHV-6 miR-aU14, a microRNA expressed only during lytic infection and reactivation that has been linked to disrupted mitochondrial function (Hennig 2022). They also used immunofluorescence to detect multiple HHV-6 antigens that are expressed at different stages of infection, as well as anti-EBV dUTPase. Finally, they used immunohistochemistry to identify cell types that displayed viral miRNA or proteins (U94, OHV-3, 6 gB, p41).

Two of the three ME/CFS patients had evidence of abundant miRNA or antigens in various brain astrocytes (in choroid plexus, hippocampus, amygdala, temporal lobe) as well as in cervical, lumbar and sacral nerve roots. This was not true in a third ME/CFS patient nor in any of the 24 control subjects. The results of the various different HHV-6 markers also were not always concordant. Evidence of EBV dUTPase also was found in some specimens from all three ME/CFS patients. Finally, there was no evidence of HHV-6 infection in Purkinje cells of the cerebellum, as has previously been reported in people with bipolar disorder (Prusty 2019).

The autopsy specimens were collected by the Cambridge Brain Bank, in part due to the efforts of a pioneering neuropathologist DG O’Donovan at Addenbrooke Hospital in Cambridge. O’Donovan examined the spinal tissue from a ME/CFS patient Sophia Mirza who was the first patient in the UK to have ME/CFS listed as a cause of death. He found dorsal root ganglionitis and later reported finding inflammation of the dorsal root ganglia in three of four ME/CFS autopsy specimens examined. As a result, O’Donovon worked hard to get additional ME/CFS cases contributed to the brain bank. Dorsal root ganglionitis has also been found in at least five other autopsies of other patients who died with ME/CFS.

Because there likely are few autopsy specimens available from people with ME/CFS it will be hard to conduct the much larger study that is needed to pursue these provocative findings. Hopefully, this report will galvanize an attempt to organize a larger study, and to pool autopsy specimens from multiple institutions.

Read the full article: Kasimir 2022