by Cort Johnson
Unexpected synchronies are always a good sign. Many, of course, are familiar with Bob Naviaux, MD, PhD from the University of California, San Diego (UCSD). Naviaux’s metabolomic work and his Cell Danger Response (CDR) hypothesis have opened up new possible ways of understanding ME/CFS, autism and other diseases.
Bhupesh Prusty, PhD of the University of Würzburg in Germany, is newer on the scene but has been raising eyebrows with his proposal that herpesviruses like HHV-6 (and other viruses as well) may be knocking the mitochondria in ME/CFS patients for a loop.
The two authors – Prusty and Naviaux were the co-senior authors who conceived the project – teamed together to attempt to answer a question that’s been plaguing patients, doctors and researchers for years: how to tie together the energy problems in ME/CFS with the infectious onset that so many patients experience. Coming from two separate fields, Bhupesh Prusty and Bob Naviaux may have come up with a way.
They chose, what else, herpesviruses (HHV-6, HHV-7) to test their hypothesis.
Herpes viruses form a large and diverse group. Epstein-Barr virus (EBV), cytomegalovirus (CMV), and Herpes simplex viruses (HSV-1 and 2) have the ability to remain latent in the body and then explode into activity during times of stress or immunodeficiency. That has always made them a clear target in a disease largely defined by symptoms associated with infections.
The Human herpes viruses (HHV-6 and HHV-7) are a little different. Over 90% of people are infected by 3 years of age, usually through their mother’s saliva. The virus then leaves a copy of its DNA in a chromosome of a few cells, then becomes dormant. For most people, we never know if HHV-6 is reactivated or not.
Prusty and Naviaux believe this is because when HHV-6 is reactivated, it triggers cells to produce a protective factor that helps prevent other cells from getting infected (superinfected) with other viruses. This protective mechanism comes at a cost, though: mitochondrial fragmentation and a decrease in cellular energy production.
In people who don’t have ME/CFS, this phenomenon is normal and only lasts a few days at the beginning of a new infection or after exposure to certain environmental chemicals, or after physical injury. However, in ME/CFS, they believe HHV-6 infected cells continue to secrete a substance which inhibits cellular energy production, leading to fatigue, and all the other symptoms of the disease.
The very low viral loads of HHV-6 found in past ME/CFS studies have suggested that active reinfection with the virus is not an issue. A 2019 HHV-6 antibody study that turned up mostly subtle issues didn’t inspire further interest, either. (That study, it should be noted, focused mostly on late antibodies which would miss the smoldering infection that some believe may be happening.) Plus all HHV-6 serological studies to date suffer from the inability to differentiate between the more difficult to assess, and possibly more dangerous, HHV-6A and HHV-6B.
In 2018, though, Prusty, produced a controversial paper that roiled the HHV-6 research world. His cell line study suggested he’d identified very small non-coding RNA’s (sncRNA) produced by the virus in the earliest stages of reactivation, but before any virus replication occurred. The production of this sncRNA produced a signal which altered mitochondrial activity in the infected cells and caused the mitochondria to fragment. The study suggested that HHV-6 might be powering down the energy motors of the cells even as it was sitting mostly quietly in the cell. It was as if the virus was putting the cells in stasis.
If Prusty was right, you could throw the viral load data in ME/CFS right out the window: HHV-6 didn’t need to be replicating to cause something like ME/CFS – it simply needed to be a little active.
Nobody in the HHV-6 field had come up with that idea before, but Bob Naviaux in San Diego had developed a similar paradigm which proposed that the cells of ME/CFS patients had responded to infections and other stressors by getting stuck in a hypometabolic state (aka a state of hibernation or dauer, the German word for persistence).
Naviaux proposed that the stricken cells used what he called a “cell danger response” to power down their motors and redirect all energy toward cellular defense and survival, at the cost, though, of not having enough energy left over for normal cellular activity and function.
The metabolic system, in particular the mitochondria, he believed, were working hand in hand to repel invaders. In fact, in Naviaux’s paradigm, it was the metabolic or energy producing system that alerted the immune system to trouble, not the other way around.
A 2015 Nature article, which has been cited over 500 times, agreed. The study found that it only took moderate mitochondrial stress to send the cell’s antiviral defenses skyrocketing. It suggested the first goal of a pathogen was to damage, knock off, or disrupt the mitochondria of the cell it infected. Once the signs of mitochondrial damage presented themselves, however, the cell – now knowing that a pathogen was present – turned on its antiviral batteries.
Just last year, a French team showed that bacteria attempt to quickly knock out the engines powering immune cells as well. The cellular immune defense, it seems, starts with the mitochondria.
To read the rest of the article, please go to –