Interview with Dharam Ablashi: On the discovery of Human Herpes Virus 6 (HHV6) and its involvement in chronic inflammatory disease

Hoopoe · Jul 2, 2020

Dr Ablashi is one of the discoverers of human herpesvirus 6.

http://microbeminded.com/2020/06/28...-involvement-in-chronic-inflammatory-disease/

What role do you think HHV6 plays in the illness myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)?

We don’t think ME/CFS is triggered by a single pathogen; we believe it can be triggered by a number of intracellular pathogens including enterovirus, parvovirus B-19, mycoplasma pneumonia, chlamydia pneumonia, EBV, Cytomegalovirus (CMV), and HHV-6A/B and HHV-7. After the Dan Peterson and Paul Cheney first discovered HHV-6 in patients with the outbreak of ME/CFS in Incline Village Nevada in the 1980s, Dan Peterson, Anthony Komaroff, and Deidra Buchwald came to see Dr. Gallo to discuss whether HHV-6 played a role in ME/CFS. At their request, we tested the antibodies of sera or plasma from ME/CFS patients. During this process we found a subset of samples with very high antibody titers to HHV-6. Buchwald, Komaroff, and associates published a paper in 1992 that found used primary cell culture to determine that 70% of ME/CFS patients but only 20% of controls showed signs of active replication. Later in 2001, I published another paper that showed an increased level of IgM antibodies to an HHV-6 early antigen protein in ME/CFS patients. This was an assay based on a reagent produced at Gary Pearson’s lab at Georgetown, and unfortunately, this reagent is no longer available. Recently Dr. Bhupesh Prusty in Germany has shown how persistent HHV-6 infection can cause mitochondrial dysfunction, which may play a role in ME/CFS. Also, Dr. Kondo recently published very interesting data showing that a neurovirulent HHV6 latency protein plays a pathogenic role in both depression and fatigue. He previously determined that HHV-6 builds up in the saliva when the body is fatigued and says this virus finds its way to the nasal passages and then on to the olfactory bulb and brain. A latency protein he calls SITH-1 then causes hyperactivation of the HPA axis and subsequent depression and fatigue.
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What are the top mistakes that research teams can make when trying to study HHV6?
Many groups studying HHV-6A/B in chronic conditions want to look in the plasma or cerebrospinal fluid (CSF), and fail to understand that HHV-6 DNA appears in those compartments only briefly and typically only during acute reactivations. These are low copy number viruses that spread cell-to-cell. They also generate potent chemokines and cytokines, even in latency.

There may be low-level DNA detectable by nested PCR in a chronic case, but generally, qPCR, ddPCR, and RNA sequencing techniques are not able to detect low level central nervous system infections of HHV-6A/B in plasma in ME/CFS and MS patients. HHV-6 DNA levels can be extremely high in the brain, liver, or lung, with barely a trace in the plasma. So biopsy analysis is extremely important. Also, HHV-6A/B viral infections have scattered foci, multiple samples per biopsy are necessary to get a true understanding of prevalence in any organ.

Another mistake is to look at DNA in whole blood, where viruses like HHV-6B and EBV can be found in latent form. For HHV-6, this is too simplistic. It is more important to identify organ tissues where there might be active infection, or a smoldering infection – a latent infection that is still throwing off inflammatory cytokines and chemokines.

Finally, many studies fail to rule out inherited chromosomally integrated HHV-6, which occurs in 0.86% of the US population controls and 1.5 – 2% of patients. These patients will always be positive for HHV-6 DNA in the plasma and CSF, even if asymptomatic, so this condition needs to be determined. (This is easy to do by measuring HHV-6 DNA in whole blood by qPCR because there is one genome per nucleated cell, so the viral load is typically in the millions per mL.)
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Tilly · Jul 2, 2020

I have two cups of coffee already and still cant sit still we so need so much more of this.

janice · Jul 2, 2020

I find this v v interesting. I did an M.Sc project ~10 years ago now looking at betaherpes viral loads in brain tissue using RT qPCR. I only found HHV6A but I didn’t get results published cos due to ME I didn’t get to finish and had to crash out with diploma.

From what I learnt and have followed since, there is gently building interest in the latent virus’ immune modulatory effects. Plus with modern techniques along side the old “wet lab” type stuff ,advances in systems biology, big data sets in the omics, etc, etc , it’s all building up to some very interesting ideas around.

HHV6 Foundation and Dr Ablashi and Dr Prusty are all amazing and very impressive I feel.

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Interview with Dharam Ablashi: On the discovery of Human Herpes Virus 6 (HHV6) and its involvement in chronic inflammatory disease

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Interview with Dharam Ablashi: On the discovery of Human Herpes Virus 6 (HHV6) and its involvement in chronic inflammatory disease

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